Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice
Identifieur interne : 007E94 ( Main/Curation ); précédent : 007E93; suivant : 007E95Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice
Auteurs : D L Bruno ; D. Ganesamoorthy ; J. Schoumans [Suède] ; A. Bankier ; D. Coman ; M. Delatycki ; R J M. Gardner ; M. Hunter ; P A James ; P. Kannu ; G. Mcgillivray ; N. Pachter ; H. Peters ; C. Rieubland ; R. Savarirayan ; I E Scheffer [Australie] ; L. Sheffield ; T. Tan ; S M White [Australie] ; A. Yeung ; Z. Bowman ; C. Ngo ; K W Choy [Hong Kong] ; V. Cacheux [France] ; L. Wong ; D J Amor [Australie] ; H R Slater [Australie]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2009-02.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Base de données, Génétique, Homme.
English descriptors
- KwdEn :
- Abnormality, Affymetrix, Array data, Broad nose, Callosum, Case length, Chromosome, Classic microdeletion, Clinical practice, Clinical presentation, Clinical significance, Cnvs, Comparative genomic hybridisation, Congenital, Congenital heart disease, Congenital malformations, Consecutive snps, Consent process, Copy number, Copy number variations, Corpus callosum, Cryptic, Cytogenetics, Database, Deletion, Detection, Developmental delay, Diagnostic success, Different chromosomes, Dysmorphism, Fetal death, Finger clinodactyly, Genet, Genet letter, Genetic abnormalities, Genetic diagnoses, Genetics, Genome, Genome coverage, Genome microarray analysis, Genomic, Genomic variants, Growth retardation, Healthy individuals, Hereditary neuropathy, Heterozygosity, High quality databases, High resolution, Higher density arrays, Homozygosity, Hong kong, Human, Human genome, Hybridisation, Incidental findings, Initial analysis, Large mouth, Log2, Log2 intensity ratios, Loss of heterozygosity, Loss table, Magnetic resonance imaging, Major cause, Major challenge, Malformation, Median size, Mental retardation, Microarray, Microarray analysis, Microarray genome analysis, Microcephaly, Microdeletion, Microdeletion syndrome, Microdeletion syndromes, Microduplication, Microduplication syndromes, Microsatellite analysis, Mild dysmorphism, Minor dysmorphism, Mlpa, Multiple malformations, Multiplex ligation, Normal brain, Normal growth, Parental samples, Pathogenesis, Pathogenic, Pathogenic cnvs, Patient, Peer review literature, Peripheral blood samples, Phenotype, Polymorphism, Postnatal, Postnatal growth retardation, Pressure palsies, Probe amplification, Professional practice, Retardation, Royal hospital, Same deletion, Segmental loss, Segmental regions, Several examples, Short palpebral fissures, Single nucleotide polymorphism, Single nucleotide polymorphisms, Size distribution, Snp, Snps number, Specific microdeletion, Structural variation, Submucous cleft palate, Supplemental information, Supplemental table, Syndrome, Uniparental disomy, Variations.
- Teeft :
- Abnormality, Affymetrix, Array data, Broad nose, Callosum, Case length, Chromosome, Classic microdeletion, Clinical practice, Clinical presentation, Clinical significance, Cnvs, Comparative genomic hybridisation, Congenital, Congenital heart disease, Congenital malformations, Consecutive snps, Consent process, Copy number, Copy number variations, Corpus callosum, Database, Deletion, Developmental delay, Diagnostic success, Different chromosomes, Dysmorphism, Fetal death, Finger clinodactyly, Genet, Genet letter, Genetic abnormalities, Genetic diagnoses, Genome, Genome coverage, Genome microarray analysis, Genomic, Genomic variants, Growth retardation, Healthy individuals, Hereditary neuropathy, Heterozygosity, High quality databases, Higher density arrays, Homozygosity, Hong kong, Human genome, Hybridisation, Incidental findings, Initial analysis, Large mouth, Log2, Log2 intensity ratios, Loss table, Magnetic resonance imaging, Major cause, Major challenge, Malformation, Median size, Mental retardation, Microarray, Microarray analysis, Microarray genome analysis, Microcephaly, Microdeletion, Microdeletion syndrome, Microdeletion syndromes, Microduplication, Microduplication syndromes, Microsatellite analysis, Mild dysmorphism, Minor dysmorphism, Mlpa, Multiple malformations, Multiplex ligation, Normal brain, Normal growth, Parental samples, Pathogenic, Pathogenic cnvs, Peer review literature, Peripheral blood samples, Phenotype, Polymorphism, Postnatal, Postnatal growth retardation, Pressure palsies, Probe amplification, Retardation, Royal hospital, Same deletion, Segmental loss, Segmental regions, Several examples, Short palpebral fissures, Single nucleotide polymorphisms, Size distribution, Snp, Snps number, Specific microdeletion, Structural variation, Submucous cleft palate, Supplemental information, Supplemental table, Syndrome, Uniparental disomy.
Abstract
Background: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as “potentially pathogenic”. Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered “new syndromes” were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype–phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.
Url:
DOI: 10.1136/jmg.2008.062604
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D L Bruno<affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation>Le document en format XML
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Coman</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Delatycki, M" sort="Delatycki, M" uniqKey="Delatycki M" first="M" last="Delatycki">M. Delatycki</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Gardner, R J M" sort="Gardner, R J M" uniqKey="Gardner R" first="R J M" last="Gardner">R J M. Gardner</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M" last="Hunter">M. Hunter</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="James, P A" sort="James, P A" uniqKey="James P" first="P A" last="James">P A James</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Kannu, P" sort="Kannu, P" uniqKey="Kannu P" first="P" last="Kannu">P. Kannu</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Mcgillivray, G" sort="Mcgillivray, G" uniqKey="Mcgillivray G" first="G" last="Mcgillivray">G. Mcgillivray</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Pachter, N" sort="Pachter, N" uniqKey="Pachter N" first="N" last="Pachter">N. Pachter</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Peters, H" sort="Peters, H" uniqKey="Peters H" first="H" last="Peters">H. Peters</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Rieubland, C" sort="Rieubland, C" uniqKey="Rieubland C" first="C" last="Rieubland">C. Rieubland</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Savarirayan, R" sort="Savarirayan, R" uniqKey="Savarirayan R" first="R" last="Savarirayan">R. Savarirayan</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Scheffer, I E" sort="Scheffer, I E" uniqKey="Scheffer I" first="I E" last="Scheffer">I E Scheffer</name><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Sheffield, L" sort="Sheffield, L" uniqKey="Sheffield L" first="L" last="Sheffield">L. Sheffield</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Tan, T" sort="Tan, T" uniqKey="Tan T" first="T" last="Tan">T. Tan</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="White, S M" sort="White, S M" uniqKey="White S" first="S M" last="White">S M White</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Yeung, A" sort="Yeung, A" uniqKey="Yeung A" first="A" last="Yeung">A. Yeung</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Bowman, Z" sort="Bowman, Z" uniqKey="Bowman Z" first="Z" last="Bowman">Z. Bowman</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Ngo, C" sort="Ngo, C" uniqKey="Ngo C" first="C" last="Ngo">C. Ngo</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Choy, K W" sort="Choy, K W" uniqKey="Choy K" first="K W" last="Choy">K W Choy</name><affiliation wicri:level="4"><orgName type="university">Université chinoise de Hong Kong</orgName><country>Hong Kong</country><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Cacheux, V" sort="Cacheux, V" uniqKey="Cacheux V" first="V" last="Cacheux">V. Cacheux</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Médicale et Chromosomique, Hôpital Arnaud de Villeneuve, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Wong, L" sort="Wong, L" uniqKey="Wong L" first="L" last="Wong">L. Wong</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Amor, D J" sort="Amor, D J" uniqKey="Amor D" first="D J" last="Amor">D J Amor</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Slater, H R" sort="Slater, H R" uniqKey="Slater H" first="H R" last="Slater">H R Slater</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-02">2009-02</date><biblScope unit="volume">46</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="123">123</biblScope></imprint><idno type="ISSN">0022-2593</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abnormality</term><term>Affymetrix</term><term>Array data</term><term>Broad nose</term><term>Callosum</term><term>Case length</term><term>Chromosome</term><term>Classic microdeletion</term><term>Clinical practice</term><term>Clinical presentation</term><term>Clinical significance</term><term>Cnvs</term><term>Comparative genomic hybridisation</term><term>Congenital</term><term>Congenital heart disease</term><term>Congenital malformations</term><term>Consecutive snps</term><term>Consent process</term><term>Copy number</term><term>Copy number variations</term><term>Corpus callosum</term><term>Cryptic</term><term>Cytogenetics</term><term>Database</term><term>Deletion</term><term>Detection</term><term>Developmental delay</term><term>Diagnostic success</term><term>Different chromosomes</term><term>Dysmorphism</term><term>Fetal death</term><term>Finger clinodactyly</term><term>Genet</term><term>Genet letter</term><term>Genetic abnormalities</term><term>Genetic diagnoses</term><term>Genetics</term><term>Genome</term><term>Genome coverage</term><term>Genome microarray analysis</term><term>Genomic</term><term>Genomic variants</term><term>Growth retardation</term><term>Healthy individuals</term><term>Hereditary neuropathy</term><term>Heterozygosity</term><term>High quality databases</term><term>High resolution</term><term>Higher density arrays</term><term>Homozygosity</term><term>Hong kong</term><term>Human</term><term>Human genome</term><term>Hybridisation</term><term>Incidental findings</term><term>Initial analysis</term><term>Large mouth</term><term>Log2</term><term>Log2 intensity ratios</term><term>Loss of heterozygosity</term><term>Loss table</term><term>Magnetic resonance imaging</term><term>Major cause</term><term>Major challenge</term><term>Malformation</term><term>Median size</term><term>Mental retardation</term><term>Microarray</term><term>Microarray analysis</term><term>Microarray genome analysis</term><term>Microcephaly</term><term>Microdeletion</term><term>Microdeletion syndrome</term><term>Microdeletion syndromes</term><term>Microduplication</term><term>Microduplication syndromes</term><term>Microsatellite analysis</term><term>Mild dysmorphism</term><term>Minor dysmorphism</term><term>Mlpa</term><term>Multiple malformations</term><term>Multiplex ligation</term><term>Normal brain</term><term>Normal growth</term><term>Parental samples</term><term>Pathogenesis</term><term>Pathogenic</term><term>Pathogenic cnvs</term><term>Patient</term><term>Peer review literature</term><term>Peripheral blood samples</term><term>Phenotype</term><term>Polymorphism</term><term>Postnatal</term><term>Postnatal growth retardation</term><term>Pressure palsies</term><term>Probe amplification</term><term>Professional practice</term><term>Retardation</term><term>Royal hospital</term><term>Same deletion</term><term>Segmental loss</term><term>Segmental regions</term><term>Several examples</term><term>Short palpebral fissures</term><term>Single nucleotide polymorphism</term><term>Single nucleotide polymorphisms</term><term>Size distribution</term><term>Snp</term><term>Snps number</term><term>Specific microdeletion</term><term>Structural variation</term><term>Submucous cleft palate</term><term>Supplemental information</term><term>Supplemental table</term><term>Syndrome</term><term>Uniparental disomy</term><term>Variations</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cryptique</term><term>Cytogénétique</term><term>Détection</term><term>Génétique</term><term>Haute résolution</term><term>Homme</term><term>Malade</term><term>Nombre copie</term><term>Pathogène</term><term>Pathogénie</term><term>Perte hétérozygotie</term><term>Polymorphisme mononucléotide</term><term>Pratique professionnelle</term><term>Variation</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Abnormality</term><term>Affymetrix</term><term>Array data</term><term>Broad nose</term><term>Callosum</term><term>Case length</term><term>Chromosome</term><term>Classic microdeletion</term><term>Clinical practice</term><term>Clinical presentation</term><term>Clinical significance</term><term>Cnvs</term><term>Comparative genomic hybridisation</term><term>Congenital</term><term>Congenital heart disease</term><term>Congenital malformations</term><term>Consecutive snps</term><term>Consent process</term><term>Copy number</term><term>Copy number variations</term><term>Corpus callosum</term><term>Database</term><term>Deletion</term><term>Developmental delay</term><term>Diagnostic success</term><term>Different chromosomes</term><term>Dysmorphism</term><term>Fetal death</term><term>Finger clinodactyly</term><term>Genet</term><term>Genet letter</term><term>Genetic abnormalities</term><term>Genetic diagnoses</term><term>Genome</term><term>Genome coverage</term><term>Genome microarray analysis</term><term>Genomic</term><term>Genomic variants</term><term>Growth retardation</term><term>Healthy individuals</term><term>Hereditary neuropathy</term><term>Heterozygosity</term><term>High quality databases</term><term>Higher density arrays</term><term>Homozygosity</term><term>Hong kong</term><term>Human genome</term><term>Hybridisation</term><term>Incidental findings</term><term>Initial analysis</term><term>Large mouth</term><term>Log2</term><term>Log2 intensity ratios</term><term>Loss table</term><term>Magnetic resonance imaging</term><term>Major cause</term><term>Major challenge</term><term>Malformation</term><term>Median size</term><term>Mental retardation</term><term>Microarray</term><term>Microarray analysis</term><term>Microarray genome analysis</term><term>Microcephaly</term><term>Microdeletion</term><term>Microdeletion syndrome</term><term>Microdeletion syndromes</term><term>Microduplication</term><term>Microduplication syndromes</term><term>Microsatellite analysis</term><term>Mild dysmorphism</term><term>Minor dysmorphism</term><term>Mlpa</term><term>Multiple malformations</term><term>Multiplex ligation</term><term>Normal brain</term><term>Normal growth</term><term>Parental samples</term><term>Pathogenic</term><term>Pathogenic cnvs</term><term>Peer review literature</term><term>Peripheral blood samples</term><term>Phenotype</term><term>Polymorphism</term><term>Postnatal</term><term>Postnatal growth retardation</term><term>Pressure palsies</term><term>Probe amplification</term><term>Retardation</term><term>Royal hospital</term><term>Same deletion</term><term>Segmental loss</term><term>Segmental regions</term><term>Several examples</term><term>Short palpebral fissures</term><term>Single nucleotide polymorphisms</term><term>Size distribution</term><term>Snp</term><term>Snps number</term><term>Specific microdeletion</term><term>Structural variation</term><term>Submucous cleft palate</term><term>Supplemental information</term><term>Supplemental table</term><term>Syndrome</term><term>Uniparental disomy</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Base de données</term><term>Génétique</term><term>Homme</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as “potentially pathogenic”. Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered “new syndromes” were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype–phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.</div></front></TEI><double idat="0022-2593:2009:Bruno D:detection:of:cryptic"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice</title><author><name sortKey="Bruno, D L" sort="Bruno, D L" uniqKey="Bruno D" first="D. L." last="Bruno">D. L. Bruno</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Ganesamoorthy, D" sort="Ganesamoorthy, D" uniqKey="Ganesamoorthy D" first="D." last="Ganesamoorthy">D. Ganesamoorthy</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Schoumans, J" sort="Schoumans, J" uniqKey="Schoumans J" first="J." last="Schoumans">J. Schoumans</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>3 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bankier, A" sort="Bankier, A" uniqKey="Bankier A" first="A." last="Bankier">A. Bankier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Coman, D" sort="Coman, D" uniqKey="Coman D" first="D." last="Coman">D. Coman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Delatycki, M" sort="Delatycki, M" uniqKey="Delatycki M" first="M." last="Delatycki">M. Delatycki</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Gardner, R J M" sort="Gardner, R J M" uniqKey="Gardner R" first="R. J. M." last="Gardner">R. J. M. Gardner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M." last="Hunter">M. Hunter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="James, P A" sort="James, P A" uniqKey="James P" first="P. A." last="James">P. A. James</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Kannu, P" sort="Kannu, P" uniqKey="Kannu P" first="P." last="Kannu">P. Kannu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Mcgillivray, G" sort="Mcgillivray, G" uniqKey="Mcgillivray G" first="G." last="Mcgillivray">G. Mcgillivray</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Pachter, N" sort="Pachter, N" uniqKey="Pachter N" first="N." last="Pachter">N. Pachter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Peters, H" sort="Peters, H" uniqKey="Peters H" first="H." last="Peters">H. Peters</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Rieubland, C" sort="Rieubland, C" uniqKey="Rieubland C" first="C." last="Rieubland">C. Rieubland</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Savarirayan, R" sort="Savarirayan, R" uniqKey="Savarirayan R" first="R." last="Savarirayan">R. Savarirayan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Scheffer, I E" sort="Scheffer, I E" uniqKey="Scheffer I" first="I. E." last="Scheffer">I. E. Scheffer</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health</s1><s2>Heidelberg, Victoria</s2><s3>AUS</s3><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Sheffield, L" sort="Sheffield, L" uniqKey="Sheffield L" first="L." last="Sheffield">L. Sheffield</name></author><author><name sortKey="Tan, T" sort="Tan, T" uniqKey="Tan T" first="T." last="Tan">T. Tan</name></author><author><name sortKey="White, S M" sort="White, S M" uniqKey="White S" first="S. M." last="White">S. M. White</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Yeung, A" sort="Yeung, A" uniqKey="Yeung A" first="A." last="Yeung">A. Yeung</name></author><author><name sortKey="Bowman, Z" sort="Bowman, Z" uniqKey="Bowman Z" first="Z." last="Bowman">Z. Bowman</name></author><author><name sortKey="Ngo, C" sort="Ngo, C" uniqKey="Ngo C" first="C." last="Ngo">C. Ngo</name></author><author><name sortKey="Choy, K W" sort="Choy, K W" uniqKey="Choy K" first="K. W." last="Choy">K. W. Choy</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Chinese University of Hong Kong</s1><s3>HKG</s3><sZ>23 aut.</sZ></inist:fA14><country>Hong Kong</country><placeName><settlement type="city">Sha Tin</settlement></placeName><orgName type="university">Université chinoise de Hong Kong</orgName></affiliation></author><author><name sortKey="Cacheux, V" sort="Cacheux, V" uniqKey="Cacheux V" first="V." last="Cacheux">V. Cacheux</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Laboratoire de Génétique Médicale et Chromosomique, Hôpital Arnaud de Villeneuve</s1><s2>Montpellier</s2><s3>FRA</s3><sZ>24 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Wong, L" sort="Wong, L" uniqKey="Wong L" first="L." last="Wong">L. Wong</name></author><author><name sortKey="Amor, D J" sort="Amor, D J" uniqKey="Amor D" first="D. J." last="Amor">D. J. Amor</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Slater, H R" sort="Slater, H R" uniqKey="Slater H" first="H. R." last="Slater">H. R. Slater</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0237292</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0237292 INIST</idno><idno type="RBID">Pascal:09-0237292</idno><idno type="wicri:Area/PascalFrancis/Corpus">002D94</idno><idno type="wicri:Area/PascalFrancis/Curation">003226</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">002C09</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">002C09</idno><idno type="wicri:doubleKey">0022-2593:2009:Bruno D:detection:of:cryptic</idno><idno type="wicri:Area/Main/Merge">008B78</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice</title><author><name sortKey="Bruno, D L" sort="Bruno, D L" uniqKey="Bruno D" first="D. L." last="Bruno">D. L. Bruno</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Ganesamoorthy, D" sort="Ganesamoorthy, D" uniqKey="Ganesamoorthy D" first="D." last="Ganesamoorthy">D. Ganesamoorthy</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Schoumans, J" sort="Schoumans, J" uniqKey="Schoumans J" first="J." last="Schoumans">J. Schoumans</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>3 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bankier, A" sort="Bankier, A" uniqKey="Bankier A" first="A." last="Bankier">A. Bankier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Coman, D" sort="Coman, D" uniqKey="Coman D" first="D." last="Coman">D. Coman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Delatycki, M" sort="Delatycki, M" uniqKey="Delatycki M" first="M." last="Delatycki">M. Delatycki</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Gardner, R J M" sort="Gardner, R J M" uniqKey="Gardner R" first="R. J. M." last="Gardner">R. J. M. Gardner</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M." last="Hunter">M. Hunter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="James, P A" sort="James, P A" uniqKey="James P" first="P. A." last="James">P. A. James</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Kannu, P" sort="Kannu, P" uniqKey="Kannu P" first="P." last="Kannu">P. Kannu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Mcgillivray, G" sort="Mcgillivray, G" uniqKey="Mcgillivray G" first="G." last="Mcgillivray">G. Mcgillivray</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Pachter, N" sort="Pachter, N" uniqKey="Pachter N" first="N." last="Pachter">N. Pachter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Peters, H" sort="Peters, H" uniqKey="Peters H" first="H." last="Peters">H. Peters</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Rieubland, C" sort="Rieubland, C" uniqKey="Rieubland C" first="C." last="Rieubland">C. Rieubland</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Savarirayan, R" sort="Savarirayan, R" uniqKey="Savarirayan R" first="R." last="Savarirayan">R. Savarirayan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Scheffer, I E" sort="Scheffer, I E" uniqKey="Scheffer I" first="I. E." last="Scheffer">I. E. Scheffer</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health</s1><s2>Heidelberg, Victoria</s2><s3>AUS</s3><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Sheffield, L" sort="Sheffield, L" uniqKey="Sheffield L" first="L." last="Sheffield">L. Sheffield</name></author><author><name sortKey="Tan, T" sort="Tan, T" uniqKey="Tan T" first="T." last="Tan">T. Tan</name></author><author><name sortKey="White, S M" sort="White, S M" uniqKey="White S" first="S. M." last="White">S. M. White</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Yeung, A" sort="Yeung, A" uniqKey="Yeung A" first="A." last="Yeung">A. Yeung</name></author><author><name sortKey="Bowman, Z" sort="Bowman, Z" uniqKey="Bowman Z" first="Z." last="Bowman">Z. Bowman</name></author><author><name sortKey="Ngo, C" sort="Ngo, C" uniqKey="Ngo C" first="C." last="Ngo">C. Ngo</name></author><author><name sortKey="Choy, K W" sort="Choy, K W" uniqKey="Choy K" first="K. W." last="Choy">K. W. Choy</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Chinese University of Hong Kong</s1><s3>HKG</s3><sZ>23 aut.</sZ></inist:fA14><country>Hong Kong</country><placeName><settlement type="city">Sha Tin</settlement></placeName><orgName type="university">Université chinoise de Hong Kong</orgName></affiliation></author><author><name sortKey="Cacheux, V" sort="Cacheux, V" uniqKey="Cacheux V" first="V." last="Cacheux">V. Cacheux</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Laboratoire de Génétique Médicale et Chromosomique, Hôpital Arnaud de Villeneuve</s1><s2>Montpellier</s2><s3>FRA</s3><sZ>24 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Wong, L" sort="Wong, L" uniqKey="Wong L" first="L." last="Wong">L. Wong</name></author><author><name sortKey="Amor, D J" sort="Amor, D J" uniqKey="Amor D" first="D. J." last="Amor">D. J. Amor</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Slater, H R" sort="Slater, H R" uniqKey="Slater H" first="H. R." last="Slater">H. R. Slater</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</s1><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victorian Clinical Genetics Services, Murdoch Children's Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>19 aut.</sZ><sZ>26 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of medical genetics</title><title level="j" type="abbreviated">J. med. genet.</title><idno type="ISSN">0022-2593</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of medical genetics</title><title level="j" type="abbreviated">J. med. genet.</title><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Copy number</term><term>Cryptic</term><term>Cytogenetics</term><term>Detection</term><term>Genetics</term><term>High resolution</term><term>Human</term><term>Loss of heterozygosity</term><term>Pathogenesis</term><term>Pathogenic</term><term>Patient</term><term>Professional practice</term><term>Single nucleotide polymorphism</term><term>Variations</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Détection</term><term>Cryptique</term><term>Pathogène</term><term>Pathogénie</term><term>Nombre copie</term><term>Variation</term><term>Perte hétérozygotie</term><term>Haute résolution</term><term>Polymorphisme mononucléotide</term><term>Homme</term><term>Malade</term><term>Cytogénétique</term><term>Pratique professionnelle</term><term>Génétique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.</div></front></TEI></INIST><ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice</title><author><name sortKey="Bruno, D L" sort="Bruno, D L" uniqKey="Bruno D" first="D L" last="Bruno">D L Bruno</name></author><author><name sortKey="Ganesamoorthy, D" sort="Ganesamoorthy, D" uniqKey="Ganesamoorthy D" first="D" last="Ganesamoorthy">D. Ganesamoorthy</name></author><author><name sortKey="Schoumans, J" sort="Schoumans, J" uniqKey="Schoumans J" first="J" last="Schoumans">J. Schoumans</name></author><author><name sortKey="Bankier, A" sort="Bankier, A" uniqKey="Bankier A" first="A" last="Bankier">A. Bankier</name></author><author><name sortKey="Coman, D" sort="Coman, D" uniqKey="Coman D" first="D" last="Coman">D. Coman</name></author><author><name sortKey="Delatycki, M" sort="Delatycki, M" uniqKey="Delatycki M" first="M" last="Delatycki">M. Delatycki</name></author><author><name sortKey="Gardner, R J M" sort="Gardner, R J M" uniqKey="Gardner R" first="R J M" last="Gardner">R J M. Gardner</name></author><author><name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M" last="Hunter">M. Hunter</name></author><author><name sortKey="James, P A" sort="James, P A" uniqKey="James P" first="P A" last="James">P A James</name></author><author><name sortKey="Kannu, P" sort="Kannu, P" uniqKey="Kannu P" first="P" last="Kannu">P. Kannu</name></author><author><name sortKey="Mcgillivray, G" sort="Mcgillivray, G" uniqKey="Mcgillivray G" first="G" last="Mcgillivray">G. Mcgillivray</name></author><author><name sortKey="Pachter, N" sort="Pachter, N" uniqKey="Pachter N" first="N" last="Pachter">N. Pachter</name></author><author><name sortKey="Peters, H" sort="Peters, H" uniqKey="Peters H" first="H" last="Peters">H. Peters</name></author><author><name sortKey="Rieubland, C" sort="Rieubland, C" uniqKey="Rieubland C" first="C" last="Rieubland">C. Rieubland</name></author><author><name sortKey="Savarirayan, R" sort="Savarirayan, R" uniqKey="Savarirayan R" first="R" last="Savarirayan">R. Savarirayan</name></author><author><name sortKey="Scheffer, I E" sort="Scheffer, I E" uniqKey="Scheffer I" first="I E" last="Scheffer">I E Scheffer</name></author><author><name sortKey="Sheffield, L" sort="Sheffield, L" uniqKey="Sheffield L" first="L" last="Sheffield">L. Sheffield</name></author><author><name sortKey="Tan, T" sort="Tan, T" uniqKey="Tan T" first="T" last="Tan">T. Tan</name></author><author><name sortKey="White, S M" sort="White, S M" uniqKey="White S" first="S M" last="White">S M White</name></author><author><name sortKey="Yeung, A" sort="Yeung, A" uniqKey="Yeung A" first="A" last="Yeung">A. Yeung</name></author><author><name sortKey="Bowman, Z" sort="Bowman, Z" uniqKey="Bowman Z" first="Z" last="Bowman">Z. Bowman</name></author><author><name sortKey="Ngo, C" sort="Ngo, C" uniqKey="Ngo C" first="C" last="Ngo">C. Ngo</name></author><author><name sortKey="Choy, K W" sort="Choy, K W" uniqKey="Choy K" first="K W" last="Choy">K W Choy</name></author><author><name sortKey="Cacheux, V" sort="Cacheux, V" uniqKey="Cacheux V" first="V" last="Cacheux">V. Cacheux</name></author><author><name sortKey="Wong, L" sort="Wong, L" uniqKey="Wong L" first="L" last="Wong">L. Wong</name></author><author><name sortKey="Amor, D J" sort="Amor, D J" uniqKey="Amor D" first="D J" last="Amor">D J Amor</name></author><author><name sortKey="Slater, H R" sort="Slater, H R" uniqKey="Slater H" first="H R" last="Slater">H R Slater</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:C9598C3CFF9D707ABF17804194F8854AB7228EF1</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1136/jmg.2008.062604</idno><idno type="url">https://api.istex.fr/document/C9598C3CFF9D707ABF17804194F8854AB7228EF1/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002549</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002549</idno><idno type="wicri:Area/Istex/Curation">002549</idno><idno type="wicri:Area/Istex/Checkpoint">000F31</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000F31</idno><idno type="wicri:doubleKey">0022-2593:2009:Bruno D:detection:of:cryptic</idno><idno type="wicri:Area/Main/Merge">008589</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice</title><author><name sortKey="Bruno, D L" sort="Bruno, D L" uniqKey="Bruno D" first="D L" last="Bruno">D L Bruno</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Ganesamoorthy, D" sort="Ganesamoorthy, D" uniqKey="Ganesamoorthy D" first="D" last="Ganesamoorthy">D. Ganesamoorthy</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Schoumans, J" sort="Schoumans, J" uniqKey="Schoumans J" first="J" last="Schoumans">J. Schoumans</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bankier, A" sort="Bankier, A" uniqKey="Bankier A" first="A" last="Bankier">A. Bankier</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Coman, D" sort="Coman, D" uniqKey="Coman D" first="D" last="Coman">D. Coman</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Delatycki, M" sort="Delatycki, M" uniqKey="Delatycki M" first="M" last="Delatycki">M. Delatycki</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Gardner, R J M" sort="Gardner, R J M" uniqKey="Gardner R" first="R J M" last="Gardner">R J M. Gardner</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M" last="Hunter">M. Hunter</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="James, P A" sort="James, P A" uniqKey="James P" first="P A" last="James">P A James</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Kannu, P" sort="Kannu, P" uniqKey="Kannu P" first="P" last="Kannu">P. Kannu</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Mcgillivray, G" sort="Mcgillivray, G" uniqKey="Mcgillivray G" first="G" last="Mcgillivray">G. Mcgillivray</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Pachter, N" sort="Pachter, N" uniqKey="Pachter N" first="N" last="Pachter">N. Pachter</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Peters, H" sort="Peters, H" uniqKey="Peters H" first="H" last="Peters">H. Peters</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Rieubland, C" sort="Rieubland, C" uniqKey="Rieubland C" first="C" last="Rieubland">C. Rieubland</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Savarirayan, R" sort="Savarirayan, R" uniqKey="Savarirayan R" first="R" last="Savarirayan">R. Savarirayan</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Scheffer, I E" sort="Scheffer, I E" uniqKey="Scheffer I" first="I E" last="Scheffer">I E Scheffer</name><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Sheffield, L" sort="Sheffield, L" uniqKey="Sheffield L" first="L" last="Sheffield">L. Sheffield</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Tan, T" sort="Tan, T" uniqKey="Tan T" first="T" last="Tan">T. Tan</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="White, S M" sort="White, S M" uniqKey="White S" first="S M" last="White">S M White</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Yeung, A" sort="Yeung, A" uniqKey="Yeung A" first="A" last="Yeung">A. Yeung</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Bowman, Z" sort="Bowman, Z" uniqKey="Bowman Z" first="Z" last="Bowman">Z. Bowman</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Ngo, C" sort="Ngo, C" uniqKey="Ngo C" first="C" last="Ngo">C. Ngo</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Choy, K W" sort="Choy, K W" uniqKey="Choy K" first="K W" last="Choy">K W Choy</name><affiliation wicri:level="4"><orgName type="university">Université chinoise de Hong Kong</orgName><country>Hong Kong</country><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Cacheux, V" sort="Cacheux, V" uniqKey="Cacheux V" first="V" last="Cacheux">V. Cacheux</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Médicale et Chromosomique, Hôpital Arnaud de Villeneuve, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Wong, L" sort="Wong, L" uniqKey="Wong L" first="L" last="Wong">L. Wong</name><affiliation><wicri:noCountry code="subField">Institute</wicri:noCountry></affiliation></author><author><name sortKey="Amor, D J" sort="Amor, D J" uniqKey="Amor D" first="D J" last="Amor">D J Amor</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Slater, H R" sort="Slater, H R" uniqKey="Slater H" first="H R" last="Slater">H R Slater</name><affiliation></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-02">2009-02</date><biblScope unit="volume">46</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="123">123</biblScope></imprint><idno type="ISSN">0022-2593</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abnormality</term><term>Affymetrix</term><term>Array data</term><term>Broad nose</term><term>Callosum</term><term>Case length</term><term>Chromosome</term><term>Classic microdeletion</term><term>Clinical practice</term><term>Clinical presentation</term><term>Clinical significance</term><term>Cnvs</term><term>Comparative genomic hybridisation</term><term>Congenital</term><term>Congenital heart disease</term><term>Congenital malformations</term><term>Consecutive snps</term><term>Consent process</term><term>Copy number</term><term>Copy number variations</term><term>Corpus callosum</term><term>Database</term><term>Deletion</term><term>Developmental delay</term><term>Diagnostic success</term><term>Different chromosomes</term><term>Dysmorphism</term><term>Fetal death</term><term>Finger clinodactyly</term><term>Genet</term><term>Genet letter</term><term>Genetic abnormalities</term><term>Genetic diagnoses</term><term>Genome</term><term>Genome coverage</term><term>Genome microarray analysis</term><term>Genomic</term><term>Genomic variants</term><term>Growth retardation</term><term>Healthy individuals</term><term>Hereditary neuropathy</term><term>Heterozygosity</term><term>High quality databases</term><term>Higher density arrays</term><term>Homozygosity</term><term>Hong kong</term><term>Human genome</term><term>Hybridisation</term><term>Incidental findings</term><term>Initial analysis</term><term>Large mouth</term><term>Log2</term><term>Log2 intensity ratios</term><term>Loss table</term><term>Magnetic resonance imaging</term><term>Major cause</term><term>Major challenge</term><term>Malformation</term><term>Median size</term><term>Mental retardation</term><term>Microarray</term><term>Microarray analysis</term><term>Microarray genome analysis</term><term>Microcephaly</term><term>Microdeletion</term><term>Microdeletion syndrome</term><term>Microdeletion syndromes</term><term>Microduplication</term><term>Microduplication syndromes</term><term>Microsatellite analysis</term><term>Mild dysmorphism</term><term>Minor dysmorphism</term><term>Mlpa</term><term>Multiple malformations</term><term>Multiplex ligation</term><term>Normal brain</term><term>Normal growth</term><term>Parental samples</term><term>Pathogenic</term><term>Pathogenic cnvs</term><term>Peer review literature</term><term>Peripheral blood samples</term><term>Phenotype</term><term>Polymorphism</term><term>Postnatal</term><term>Postnatal growth retardation</term><term>Pressure palsies</term><term>Probe amplification</term><term>Retardation</term><term>Royal hospital</term><term>Same deletion</term><term>Segmental loss</term><term>Segmental regions</term><term>Several examples</term><term>Short palpebral fissures</term><term>Single nucleotide polymorphisms</term><term>Size distribution</term><term>Snp</term><term>Snps number</term><term>Specific microdeletion</term><term>Structural variation</term><term>Submucous cleft palate</term><term>Supplemental information</term><term>Supplemental table</term><term>Syndrome</term><term>Uniparental disomy</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Abnormality</term><term>Affymetrix</term><term>Array data</term><term>Broad nose</term><term>Callosum</term><term>Case length</term><term>Chromosome</term><term>Classic microdeletion</term><term>Clinical practice</term><term>Clinical presentation</term><term>Clinical significance</term><term>Cnvs</term><term>Comparative genomic hybridisation</term><term>Congenital</term><term>Congenital heart disease</term><term>Congenital malformations</term><term>Consecutive snps</term><term>Consent process</term><term>Copy number</term><term>Copy number variations</term><term>Corpus callosum</term><term>Database</term><term>Deletion</term><term>Developmental delay</term><term>Diagnostic success</term><term>Different chromosomes</term><term>Dysmorphism</term><term>Fetal death</term><term>Finger clinodactyly</term><term>Genet</term><term>Genet letter</term><term>Genetic abnormalities</term><term>Genetic diagnoses</term><term>Genome</term><term>Genome coverage</term><term>Genome microarray analysis</term><term>Genomic</term><term>Genomic variants</term><term>Growth retardation</term><term>Healthy individuals</term><term>Hereditary neuropathy</term><term>Heterozygosity</term><term>High quality databases</term><term>Higher density arrays</term><term>Homozygosity</term><term>Hong kong</term><term>Human genome</term><term>Hybridisation</term><term>Incidental findings</term><term>Initial analysis</term><term>Large mouth</term><term>Log2</term><term>Log2 intensity ratios</term><term>Loss table</term><term>Magnetic resonance imaging</term><term>Major cause</term><term>Major challenge</term><term>Malformation</term><term>Median size</term><term>Mental retardation</term><term>Microarray</term><term>Microarray analysis</term><term>Microarray genome analysis</term><term>Microcephaly</term><term>Microdeletion</term><term>Microdeletion syndrome</term><term>Microdeletion syndromes</term><term>Microduplication</term><term>Microduplication syndromes</term><term>Microsatellite analysis</term><term>Mild dysmorphism</term><term>Minor dysmorphism</term><term>Mlpa</term><term>Multiple malformations</term><term>Multiplex ligation</term><term>Normal brain</term><term>Normal growth</term><term>Parental samples</term><term>Pathogenic</term><term>Pathogenic cnvs</term><term>Peer review literature</term><term>Peripheral blood samples</term><term>Phenotype</term><term>Polymorphism</term><term>Postnatal</term><term>Postnatal growth retardation</term><term>Pressure palsies</term><term>Probe amplification</term><term>Retardation</term><term>Royal hospital</term><term>Same deletion</term><term>Segmental loss</term><term>Segmental regions</term><term>Several examples</term><term>Short palpebral fissures</term><term>Single nucleotide polymorphisms</term><term>Size distribution</term><term>Snp</term><term>Snps number</term><term>Specific microdeletion</term><term>Structural variation</term><term>Submucous cleft palate</term><term>Supplemental information</term><term>Supplemental table</term><term>Syndrome</term><term>Uniparental disomy</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Base de données</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as “potentially pathogenic”. Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered “new syndromes” were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype–phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.</div></front></TEI></ISTEX></double></record>Pour manipuler ce document sous Unix (Dilib)
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