X‐linked Opitz syndrome: Novel mutations in the MID1 gene and redefinition of the clinical spectrum
Identifieur interne : 002D96 ( Istex/Corpus ); précédent : 002D95; suivant : 002D97X‐linked Opitz syndrome: Novel mutations in the MID1 gene and redefinition of the clinical spectrum
Auteurs : Francesca De Falco ; Silvia Cainarca ; Grazia Andolfi ; Rosa Ferrentino ; Caterina Berti ; German Rodríguez Criado ; Olaf Rittinger ; Nick Dennis ; Sylvie Odent ; Amit Rastogi ; Jan Liebelt ; David Chitayat ; Robin Winter ; Harindar Jawanda ; Andrea Ballabio ; Brunella Franco ; Germana MeroniSource :
- American Journal of Medical Genetics Part A [ 1552-4825 ] ; 2003-07-15.
English descriptors
- KwdEn :
- Abnormality, Anomaly, Anus, Bilateral cleft, Cleft, Corpus callosum, Defect, Developmental delay, Gaudenz, Genet, Hypertelorism, Hypoplastic scrotum, Hypospadias, Imperforate anus, Laryngeal, Laryngeal cleft, Main manifestations, Mid1, Mid1 gene, Mid1 mutations, Midline, Monozygotic twins, Mutation, Mutation analysis, Novel mutations, Opitz, Opitz syndrome, Palate, Pedigree, Phenotype, Quaderi, Robin, Same mutation, Sporadic patient, Syndrome, Xlos.
- Teeft :
- Abnormality, Anomaly, Anus, Bilateral cleft, Cleft, Corpus callosum, Defect, Developmental delay, Gaudenz, Genet, Hypertelorism, Hypoplastic scrotum, Hypospadias, Imperforate anus, Laryngeal, Laryngeal cleft, Main manifestations, Mid1, Mid1 gene, Mid1 mutations, Midline, Monozygotic twins, Mutation, Mutation analysis, Novel mutations, Opitz, Opitz syndrome, Palate, Pedigree, Phenotype, Quaderi, Robin, Same mutation, Sporadic patient, Syndrome, Xlos.
Abstract
Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MID1, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MID1 gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the MID1‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all MID1‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a MID1‐mutated patient showing syndactyly. The low frequency of mutations in MID1 and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/ajmg.a.10265
Links to Exploration step
ISTEX:F4004711B97E5C199F9A786C7CD83763964A7069Le document en format XML
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Italy</mods:affiliation></affiliation></author><author><name sortKey="Meroni, Germana" sort="Meroni, Germana" uniqKey="Meroni G" first="Germana" last="Meroni">Germana Meroni</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: meroni@tigem.it</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: TIGEM (Telethon Institute of Genetics and Medicine), Via Pietro Castellino, 111, 80131 Naples, Italy.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:F4004711B97E5C199F9A786C7CD83763964A7069</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1002/ajmg.a.10265</idno><idno type="url">https://api.istex.fr/document/F4004711B97E5C199F9A786C7CD83763964A7069/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002D96</idno><idno type="wicri:explorRef" 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sortKey="Andolfi, Grazia" sort="Andolfi, Grazia" uniqKey="Andolfi G" first="Grazia" last="Andolfi">Grazia Andolfi</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: San Raffaele Telethon Institute for Gene Therapy (HSR‐TIGET), Milan, Italy.</mods:affiliation></affiliation></author><author><name sortKey="Ferrentino, Rosa" sort="Ferrentino, Rosa" uniqKey="Ferrentino R" first="Rosa" last="Ferrentino">Rosa Ferrentino</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Berti, Caterina" sort="Berti, Caterina" uniqKey="Berti C" first="Caterina" last="Berti">Caterina Berti</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Rodriguez Criado, German" sort="Rodriguez Criado, German" uniqKey="Rodriguez Criado G" first="German" last="Rodríguez Criado">German Rodríguez Criado</name><affiliation><mods:affiliation>Unidad de Dismorfología, Hospital Virgen del Rocío, Seville, Spain</mods:affiliation></affiliation></author><author><name sortKey="Rittinger, Olaf" sort="Rittinger, Olaf" uniqKey="Rittinger O" first="Olaf" last="Rittinger">Olaf Rittinger</name><affiliation><mods:affiliation>Klinische Genetik am Kinderspital, St.‐Johanns‐Spital, Salzburg, Austria</mods:affiliation></affiliation></author><author><name sortKey="Dennis, Nick" sort="Dennis, Nick" uniqKey="Dennis N" first="Nick" last="Dennis">Nick Dennis</name><affiliation><mods:affiliation>Division of Human Genetics, Princess Anne Hospital Southampton, Southampton, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Odent, Sylvie" sort="Odent, Sylvie" uniqKey="Odent S" first="Sylvie" last="Odent">Sylvie Odent</name><affiliation><mods:affiliation>Génétique médicale, Hopital Pontchaillou, Rennes, France</mods:affiliation></affiliation></author><author><name sortKey="Rastogi, Amit" sort="Rastogi, Amit" uniqKey="Rastogi A" first="Amit" last="Rastogi">Amit Rastogi</name><affiliation><mods:affiliation>McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Liebelt, Jan" sort="Liebelt, Jan" uniqKey="Liebelt J" first="Jan" last="Liebelt">Jan Liebelt</name><affiliation><mods:affiliation>Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia</mods:affiliation></affiliation></author><author><name sortKey="Chitayat, David" sort="Chitayat, David" uniqKey="Chitayat D" first="David" last="Chitayat">David Chitayat</name><affiliation><mods:affiliation>The Hospital for Sick Children, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Winter, Robin" sort="Winter, Robin" uniqKey="Winter R" first="Robin" last="Winter">Robin Winter</name><affiliation><mods:affiliation>Department of Clinical and Molecular Genetics, Institute of Child Health, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Jawanda, Harindar" sort="Jawanda, Harindar" uniqKey="Jawanda H" first="Harindar" last="Jawanda">Harindar Jawanda</name><affiliation><mods:affiliation>Children's and Women's Hospital, Vancouver, Canada</mods:affiliation></affiliation></author><author><name sortKey="Ballabio, Andrea" sort="Ballabio, Andrea" uniqKey="Ballabio A" first="Andrea" last="Ballabio">Andrea Ballabio</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Franco, Brunella" sort="Franco, Brunella" uniqKey="Franco B" first="Brunella" last="Franco">Brunella Franco</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation></author><author><name sortKey="Meroni, Germana" sort="Meroni, Germana" uniqKey="Meroni G" first="Germana" last="Meroni">Germana Meroni</name><affiliation><mods:affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: meroni@tigem.it</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: TIGEM (Telethon Institute of Genetics and Medicine), Via Pietro Castellino, 111, 80131 Naples, Italy.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">American Journal of Medical Genetics Part A</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS</title><idno type="ISSN">1552-4825</idno><idno type="eISSN">1552-4833</idno><imprint><biblScope unit="vol">120A</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="222">222</biblScope><biblScope unit="page" to="228">228</biblScope><biblScope unit="page-count">7</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2003-07-15">2003-07-15</date></imprint><idno type="ISSN">1552-4825</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4825</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abnormality</term><term>Anomaly</term><term>Anus</term><term>Bilateral cleft</term><term>Cleft</term><term>Corpus callosum</term><term>Defect</term><term>Developmental delay</term><term>Gaudenz</term><term>Genet</term><term>Hypertelorism</term><term>Hypoplastic scrotum</term><term>Hypospadias</term><term>Imperforate anus</term><term>Laryngeal</term><term>Laryngeal cleft</term><term>Main manifestations</term><term>Mid1</term><term>Mid1 gene</term><term>Mid1 mutations</term><term>Midline</term><term>Monozygotic twins</term><term>Mutation</term><term>Mutation analysis</term><term>Novel mutations</term><term>Opitz</term><term>Opitz syndrome</term><term>Palate</term><term>Pedigree</term><term>Phenotype</term><term>Quaderi</term><term>Robin</term><term>Same mutation</term><term>Sporadic patient</term><term>Syndrome</term><term>Xlos</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Abnormality</term><term>Anomaly</term><term>Anus</term><term>Bilateral cleft</term><term>Cleft</term><term>Corpus callosum</term><term>Defect</term><term>Developmental delay</term><term>Gaudenz</term><term>Genet</term><term>Hypertelorism</term><term>Hypoplastic scrotum</term><term>Hypospadias</term><term>Imperforate anus</term><term>Laryngeal</term><term>Laryngeal cleft</term><term>Main manifestations</term><term>Mid1</term><term>Mid1 gene</term><term>Mid1 mutations</term><term>Midline</term><term>Monozygotic twins</term><term>Mutation</term><term>Mutation analysis</term><term>Novel mutations</term><term>Opitz</term><term>Opitz syndrome</term><term>Palate</term><term>Pedigree</term><term>Phenotype</term><term>Quaderi</term><term>Robin</term><term>Same mutation</term><term>Sporadic patient</term><term>Syndrome</term><term>Xlos</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MID1, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MID1 gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the MID1‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all MID1‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a MID1‐mutated patient showing syndactyly. The low frequency of mutations in MID1 and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>mutation</json:string><json:string>mid1</json:string><json:string>opitz</json:string><json:string>hypospadias</json:string><json:string>hypertelorism</json:string><json:string>opitz syndrome</json:string><json:string>xlos</json:string><json:string>genet</json:string><json:string>abnormality</json:string><json:string>laryngeal</json:string><json:string>gaudenz</json:string><json:string>mid1 gene</json:string><json:string>midline</json:string><json:string>quaderi</json:string><json:string>syndrome</json:string><json:string>anus</json:string><json:string>phenotype</json:string><json:string>laryngeal cleft</json:string><json:string>anomaly</json:string><json:string>cleft</json:string><json:string>defect</json:string><json:string>novel mutations</json:string><json:string>mutation analysis</json:string><json:string>same mutation</json:string><json:string>developmental delay</json:string><json:string>monozygotic twins</json:string><json:string>bilateral cleft</json:string><json:string>mid1 mutations</json:string><json:string>corpus callosum</json:string><json:string>hypoplastic scrotum</json:string><json:string>imperforate anus</json:string><json:string>main manifestations</json:string><json:string>sporadic patient</json:string><json:string>robin</json:string><json:string>palate</json:string><json:string>pedigree</json:string></teeft></keywords><author><json:item><name>Francesca De Falco</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string></affiliations></json:item><json:item><name>Silvia Cainarca</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string><json:string>Current Address: San Raffaele Scientific Institute, Milan, Italy.</json:string></affiliations></json:item><json:item><name>Grazia Andolfi</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string><json:string>Current Address: San Raffaele Telethon Institute for Gene Therapy (HSR‐TIGET), Milan, Italy.</json:string></affiliations></json:item><json:item><name>Rosa Ferrentino</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string></affiliations></json:item><json:item><name>Caterina Berti</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string></affiliations></json:item><json:item><name>German Rodríguez Criado</name><affiliations><json:string>Unidad de Dismorfología, Hospital Virgen del Rocío, Seville, Spain</json:string></affiliations></json:item><json:item><name>Olaf Rittinger</name><affiliations><json:string>Klinische Genetik am Kinderspital, St.‐Johanns‐Spital, Salzburg, Austria</json:string></affiliations></json:item><json:item><name>Nick Dennis</name><affiliations><json:string>Division of Human Genetics, Princess Anne Hospital Southampton, Southampton, United Kingdom</json:string></affiliations></json:item><json:item><name>Sylvie Odent</name><affiliations><json:string>Génétique médicale, Hopital Pontchaillou, Rennes, France</json:string></affiliations></json:item><json:item><name>Amit Rastogi</name><affiliations><json:string>McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland</json:string></affiliations></json:item><json:item><name>Jan Liebelt</name><affiliations><json:string>Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia</json:string></affiliations></json:item><json:item><name>David Chitayat</name><affiliations><json:string>The Hospital for Sick Children, University of Toronto, Toronto, Canada</json:string></affiliations></json:item><json:item><name>Robin Winter</name><affiliations><json:string>Department of Clinical and Molecular Genetics, Institute of Child Health, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Harindar Jawanda</name><affiliations><json:string>Children's and Women's Hospital, Vancouver, Canada</json:string></affiliations></json:item><json:item><name>Andrea Ballabio</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string></affiliations></json:item><json:item><name>Brunella Franco</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string></affiliations></json:item><json:item><name>Germana Meroni</name><affiliations><json:string>Telethon Institute of Genetics and Medicine, Naples, Italy</json:string><json:string>E-mail: meroni@tigem.it</json:string><json:string>Correspondence address: TIGEM (Telethon Institute of Genetics and Medicine), Via Pietro Castellino, 111, 80131 Naples, Italy.</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Opitz syndrome</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MID1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>midline defects</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>X‐chromosome</value></json:item></subject><articleId><json:string>AJMG10265</json:string></articleId><arkIstex>ark:/67375/WNG-DTMB8QJW-K</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MID1, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MID1 gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the MID1‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all MID1‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a MID1‐mutated patient showing syndactyly. The low frequency of mutations in MID1 and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>8.782</score><pdfWordCount>4166</pdfWordCount><pdfCharCount>25865</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>218</abstractWordCount><abstractCharCount>1450</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>X‐linked Opitz syndrome: Novel mutations in the MID1 gene and redefinition of the clinical spectrum</title><pmid><json:string>12833403</json:string></pmid><genre><json:string>article</json:string></genre><host><title>American Journal of Medical Genetics Part A</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1552-4833</json:string></doi><issn><json:string>1552-4825</json:string></issn><eissn><json:string>1552-4833</json:string></eissn><publisherId><json:string>AJMG</json:string></publisherId><volume>120A</volume><issue>2</issue><pages><first>222</first><last>228</last><total>7</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Research Article</value></json:item></subject></host><namedEntities><unitex><date><json:string>2003</json:string></date><geogName></geogName><orgName><json:string>Telethon Institute of Genetics and Medicine</json:string><json:string>Princess Anne Hospital Southampton, Southampton, United Kingdom</json:string><json:string>Hospital Virgen</json:string><json:string>Institute of Child Health, London, United Kingdom</json:string><json:string>Division of Human Genetics</json:string><json:string>Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland</json:string><json:string>Italy Unidad</json:string><json:string>France Ge</json:string><json:string>Department of Clinical and Molecular Genetics</json:string><json:string>Women’s Hospital, Vancouver, Canada</json:string><json:string>Children’s Hospital, Adelaide, Australia</json:string><json:string>Hospital for Sick Children, University of Toronto, Toronto, Canada</json:string><json:string>Wiley-Liss, Inc</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Grazia Andol</json:string><json:string>David Chitayat</json:string><json:string>Robin Winter</json:string><json:string>Silvia Cainarca</json:string><json:string>Andreas Gal</json:string><json:string>I. Summary</json:string><json:string>Giancarlo Parenti</json:string><json:string>Jan Liebelt</json:string><json:string>Maria Teresa</json:string><json:string>Olaf Rittinger</json:string><json:string>Elena Rugarli</json:string><json:string>Nancy Braverman</json:string><json:string>Rosa Ferrentino</json:string><json:string>Nick Dennis</json:string><json:string>German Rodr</json:string><json:string>Sylvie Odent</json:string><json:string>Caterina Berti</json:string><json:string>By</json:string><json:string>Andrea Ballabio</json:string><json:string>Germana Meroni</json:string></persName><placeName><json:string>Austria</json:string><json:string>Rennes</json:string><json:string>Seville</json:string><json:string>Spain</json:string><json:string>Salzburg</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Gaudenz et al., 1998</json:string><json:string>Robin et al. [1996]</json:string><json:string>Quaderi et al., 1997</json:string><json:string>Liu et al., 2001</json:string><json:string>Opitz et al., 1969a,b</json:string><json:string>Robin et al., 1996</json:string><json:string>Gaudenz et al. [1998]</json:string><json:string>Trockenbacher et al., 2001</json:string><json:string>Robin et al., 1995</json:string><json:string>Cox et al., 2000</json:string><json:string>Short et al., 2002</json:string><json:string>Cox et al. [2000]</json:string><json:string>Schweiger et al., 1999</json:string><json:string>Reymond et al., 2001</json:string><json:string>Cordero and Holmes, 1978</json:string><json:string>Brooks et al., 1992</json:string><json:string>Jacobson et al., 1998</json:string><json:string>Guion-Almeida and Richieri-Costa, 1992</json:string><json:string>Robin et al.</json:string><json:string>MacDonald et al., 1993</json:string><json:string>Cainarca et al., 1999</json:string><json:string>De Falco et al.</json:string><json:string>[1998]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-DTMB8QJW-K</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - genetics & heredity</json:string></wos><scienceMetrix></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Genetics(clinical)</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - 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spectrum</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><licence>Copyright © 2003 Wiley‐Liss, Inc.</licence></availability><date type="published" when="2003-07-15"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">X‐linked Opitz syndrome: Novel mutations in the <hi rend="italic">MID1</hi> gene and redefinition of the clinical spectrum</title><title level="a" type="short" xml:lang="en">MID1 Mutations in X‐Linked Opitz Syndrome</title><author xml:id="author-0000"><persName><forename type="first">Francesca</forename><surname>De Falco</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">Silvia</forename><surname>Cainarca</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation><affiliation>Current Address: San Raffaele Scientific Institute, Milan, Italy.<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Grazia</forename><surname>Andolfi</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation><affiliation>Current Address: San Raffaele Telethon Institute for Gene Therapy (HSR‐TIGET), Milan, Italy.<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Rosa</forename><surname>Ferrentino</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Caterina</forename><surname>Berti</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">German</forename><surname>Rodríguez Criado</surname></persName><affiliation>Unidad de Dismorfología, Hospital Virgen del Rocío, Seville, Spain<address><country key="ES"></country></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">Olaf</forename><surname>Rittinger</surname></persName><affiliation>Klinische Genetik am Kinderspital, St.‐Johanns‐Spital, Salzburg, Austria<address><country key="AT"></country></address></affiliation></author><author xml:id="author-0007"><persName><forename type="first">Nick</forename><surname>Dennis</surname></persName><affiliation>Division of Human Genetics, Princess Anne Hospital Southampton, Southampton, United Kingdom<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0008"><persName><forename type="first">Sylvie</forename><surname>Odent</surname></persName><affiliation>Génétique médicale, Hopital Pontchaillou, Rennes, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0009"><persName><forename type="first">Amit</forename><surname>Rastogi</surname></persName><affiliation>McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland<address><country key="US"></country></address></affiliation></author><author xml:id="author-0010"><persName><forename type="first">Jan</forename><surname>Liebelt</surname></persName><affiliation>Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia<address><country key="AU"></country></address></affiliation></author><author xml:id="author-0011"><persName><forename type="first">David</forename><surname>Chitayat</surname></persName><affiliation>The Hospital for Sick Children, University of Toronto, Toronto, Canada<address><country key="CA"></country></address></affiliation></author><author xml:id="author-0012"><persName><forename type="first">Robin</forename><surname>Winter</surname></persName><affiliation>Department of Clinical and Molecular Genetics, Institute of Child Health, London, United Kingdom<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0013"><persName><forename type="first">Harindar</forename><surname>Jawanda</surname></persName><affiliation>Children's and Women's Hospital, Vancouver, Canada<address><country key="CA"></country></address></affiliation></author><author xml:id="author-0014"><persName><forename type="first">Andrea</forename><surname>Ballabio</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0015"><persName><forename type="first">Brunella</forename><surname>Franco</surname></persName><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation></author><author xml:id="author-0016" role="corresp"><persName><forename type="first">Germana</forename><surname>Meroni</surname></persName><email>meroni@tigem.it</email><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy<address><country key="IT"></country></address></affiliation><affiliation>TIGEM (Telethon Institute of Genetics and Medicine), Via Pietro Castellino, 111, 80131 Naples, Italy.</affiliation></author><idno type="istex">F4004711B97E5C199F9A786C7CD83763964A7069</idno><idno type="ark">ark:/67375/WNG-DTMB8QJW-K</idno><idno type="DOI">10.1002/ajmg.a.10265</idno><idno type="unit">AJMG10265</idno><idno type="toTypesetVersion">file:AJMG.AJMG10265.pdf</idno></analytic><monogr><title level="j" type="main">American Journal of Medical Genetics Part A</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS</title><idno type="pISSN">1552-4825</idno><idno type="eISSN">1552-4833</idno><idno type="book-DOI">10.1002/(ISSN)1552-4833</idno><idno type="book-part-DOI">10.1002/ajmg.a.v120a:2</idno><idno type="product">AJMG</idno><imprint><biblScope unit="vol">120A</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="222">222</biblScope><biblScope unit="page" to="228">228</biblScope><biblScope unit="page-count">7</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2003-07-15"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, <hi rend="italic">MID1</hi>, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the <hi rend="italic">MID1</hi> gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the <hi rend="italic">MID1</hi>‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all <hi rend="italic">MID1</hi>‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a <hi rend="italic">MID1</hi>‐mutated patient showing syndactyly. The low frequency of mutations in <hi rend="italic">MID1</hi> and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">Opitz syndrome</term><term xml:id="kwd2"><hi rend="italic">MID1</hi></term><term xml:id="kwd3">midline defects</term><term xml:id="kwd4">X‐chromosome</term></keywords><keywords rend="articleCategory"><term>Research Article</term></keywords><keywords rend="tocHeading1"><term>Research Articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/F4004711B97E5C199F9A786C7CD83763964A7069/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1552-4833</doi><issn type="print">1552-4825</issn><issn type="electronic">1552-4833</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS">American Journal of Medical Genetics Part A</title><title type="short">Am. 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xml:id="kwd2"><i>MID1</i></keyword><keyword xml:id="kwd3">midline defects</keyword><keyword xml:id="kwd4">X‐chromosome</keyword></keywordGroup><fundingInfo><fundingAgency>Italian Telethon Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>March of Dimes Birth Defects Foundation</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, <i>MID1</i>, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the <i>MID1</i> gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the <i>MID1</i>‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all <i>MID1</i>‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a <i>MID1</i>‐mutated patient showing syndactyly. The low frequency of mutations in <i>MID1</i> and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>X‐linked Opitz syndrome: Novel mutations in the MID1 gene and redefinition of the clinical spectrum</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>MID1 Mutations in X‐Linked Opitz Syndrome</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>X‐linked Opitz syndrome: Novel mutations in the MID1 gene and redefinition of the clinical spectrum</title></titleInfo><name type="personal"><namePart type="given">Francesca</namePart><namePart type="family">De Falco</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Silvia</namePart><namePart type="family">Cainarca</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><affiliation>Current Address: San Raffaele Scientific Institute, Milan, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Grazia</namePart><namePart type="family">Andolfi</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><affiliation>Current Address: San Raffaele Telethon Institute for Gene Therapy (HSR‐TIGET), Milan, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rosa</namePart><namePart type="family">Ferrentino</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Caterina</namePart><namePart type="family">Berti</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">German</namePart><namePart type="family">Rodríguez Criado</namePart><affiliation>Unidad de Dismorfología, Hospital Virgen del Rocío, Seville, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olaf</namePart><namePart type="family">Rittinger</namePart><affiliation>Klinische Genetik am Kinderspital, St.‐Johanns‐Spital, Salzburg, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nick</namePart><namePart type="family">Dennis</namePart><affiliation>Division of Human Genetics, Princess Anne Hospital Southampton, Southampton, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sylvie</namePart><namePart type="family">Odent</namePart><affiliation>Génétique médicale, Hopital Pontchaillou, Rennes, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Amit</namePart><namePart type="family">Rastogi</namePart><affiliation>McKusick‐Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan</namePart><namePart type="family">Liebelt</namePart><affiliation>Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Chitayat</namePart><affiliation>The Hospital for Sick Children, University of Toronto, Toronto, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robin</namePart><namePart type="family">Winter</namePart><affiliation>Department of Clinical and Molecular Genetics, Institute of Child Health, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Harindar</namePart><namePart type="family">Jawanda</namePart><affiliation>Children's and Women's Hospital, Vancouver, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrea</namePart><namePart type="family">Ballabio</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Brunella</namePart><namePart type="family">Franco</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Germana</namePart><namePart type="family">Meroni</namePart><affiliation>Telethon Institute of Genetics and Medicine, Naples, Italy</affiliation><affiliation>E-mail: meroni@tigem.it</affiliation><affiliation>Correspondence address: TIGEM (Telethon Institute of Genetics and Medicine), Via Pietro Castellino, 111, 80131 Naples, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2003-07-15</dateIssued><dateCaptured encoding="w3cdtf">2002-07-18</dateCaptured><dateValid encoding="w3cdtf">2002-12-02</dateValid><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">1</extent><extent unit="references">20</extent><extent unit="words">4960</extent></physicalDescription><abstract lang="en">Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X‐linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MID1, encodes a protein containing a RING‐Bbox‐Coiled‐coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MID1 gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X‐linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3′ region. By reviewing all the MID1‐mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo‐tracheo‐esophageal (LTE) defects are also common anomalies, being manifested by all MID1‐mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a MID1‐mutated patient showing syndactyly. The low frequency of mutations in MID1 and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. © 2003 Wiley‐Liss, Inc.</abstract><note type="funding">Italian Telethon Foundation</note><note type="funding">March of Dimes Birth Defects Foundation</note><subject lang="en"><genre>keywords</genre><topic>Opitz syndrome</topic><topic>MID1</topic><topic>midline defects</topic><topic>X‐chromosome</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part A</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1552-4825</identifier><identifier type="eISSN">1552-4833</identifier><identifier type="DOI">10.1002/(ISSN)1552-4833</identifier><identifier type="PublisherID">AJMG</identifier><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>120A</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>222</start><end>228</end><total>7</total></extent></part></relatedItem><identifier type="istex">F4004711B97E5C199F9A786C7CD83763964A7069</identifier><identifier type="ark">ark:/67375/WNG-DTMB8QJW-K</identifier><identifier type="DOI">10.1002/ajmg.a.10265</identifier><identifier type="ArticleID">AJMG10265</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2003 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/F4004711B97E5C199F9A786C7CD83763964A7069/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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