The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2
Identifieur interne : 001007 ( Istex/Corpus ); précédent : 001006; suivant : 001008The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2
Auteurs : M E Baser ; L. Kuramoto ; R. Woods ; H. Joe ; J M Friedman ; A J Wallace ; R T Ramsden ; S. Olschwang ; E. Bijlsma ; M. Kalamarides ; L. Papi ; R. Kato ; J. Carroll ; C. Lázaro ; F. Joncourt ; D M Parry ; G A Rouleau ; D G R. EvansSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2005-07.
English descriptors
- KwdEn :
- Amino, Amino terminal domain, Baser, Carboxy, Carboxy terminal domain, Covariates, Database, Deletion, Different regions, Equal groups, Exon, Exon number, Fewer meningiomas, Frameshift, Frameshift mutations, Friedman, Functional domains, Genet, Helical domain, Intracranial, Intracranial meningiomas, Intrafamilial, Kluwe, Kuramoto, Large deletions, Mautner, Meningioma, Merlin, Missense, Missense mutations, Molecular level, Mosaicism, Mutation, NF2, Nearest exon, Neurofibromatosis, Neurofibromatosis type, Nonsense mutations, Other covariates, Phenotype, Polyposis, Present study, Pulst, Ramsden, Reference group, Rouleau, Schwannomas, Severe disease, Single class, Somatic, Somatic mosaicism, Somatic mosaics, Splice, Splice site, Splice site mutations, Suppressor, Symptom, Tumour, Vestibular, genotype-phenotype correlation, neurofibromatosis 2, splice site mutation.
- Teeft :
- Amino, Amino terminal domain, Baser, Carboxy, Carboxy terminal domain, Covariates, Database, Deletion, Different regions, Equal groups, Exon, Exon number, Fewer meningiomas, Frameshift, Frameshift mutations, Friedman, Functional domains, Genet, Helical domain, Intracranial, Intracranial meningiomas, Intrafamilial, Kluwe, Kuramoto, Large deletions, Mautner, Meningioma, Merlin, Missense, Missense mutations, Molecular level, Mosaicism, Mutation, Nearest exon, Neurofibromatosis, Neurofibromatosis type, Nonsense mutations, Other covariates, Phenotype, Polyposis, Present study, Pulst, Ramsden, Reference group, Rouleau, Schwannomas, Severe disease, Single class, Somatic, Somatic mosaicism, Somatic mosaics, Splice, Splice site, Splice site mutations, Suppressor, Symptom, Tumour, Vestibular.
Abstract
Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.
Url:
DOI: 10.1136/jmg.2004.029504
Links to Exploration step
ISTEX:5548BF6B4BF8D456AABF42A94A5E2B61B7E26056Le document en format XML
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Kuramoto</name><affiliation><mods:affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Woods, R" sort="Woods, R" uniqKey="Woods R" first="R" last="Woods">R. Woods</name><affiliation><mods:affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Joe, H" sort="Joe, H" uniqKey="Joe H" first="H" last="Joe">H. Joe</name><affiliation><mods:affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Friedman, J M" sort="Friedman, J M" uniqKey="Friedman J" first="J M" last="Friedman">J M Friedman</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Wallace, A J" sort="Wallace, A J" uniqKey="Wallace A" first="A J" last="Wallace">A J Wallace</name><affiliation><mods:affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</mods:affiliation></affiliation></author><author><name sortKey="Ramsden, R T" sort="Ramsden, R T" uniqKey="Ramsden R" first="R T" last="Ramsden">R T Ramsden</name><affiliation><mods:affiliation>Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK</mods:affiliation></affiliation></author><author><name sortKey="Olschwang, S" sort="Olschwang, S" uniqKey="Olschwang S" first="S" last="Olschwang">S. Olschwang</name><affiliation><mods:affiliation>INSERM U434, Fondation Jean-Dausset-CEPH, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bijlsma, E" sort="Bijlsma, E" uniqKey="Bijlsma E" first="E" last="Bijlsma">E. Bijlsma</name><affiliation><mods:affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Kalamarides, M" sort="Kalamarides, M" uniqKey="Kalamarides M" first="M" last="Kalamarides">M. Kalamarides</name><affiliation><mods:affiliation>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</mods:affiliation></affiliation></author><author><name sortKey="Papi, L" sort="Papi, L" uniqKey="Papi L" first="L" last="Papi">L. Papi</name><affiliation><mods:affiliation>Department of Clinical Physiopathology, University of Florence, Florence, Italy</mods:affiliation></affiliation></author><author><name sortKey="Kato, R" sort="Kato, R" uniqKey="Kato R" first="R" last="Kato">R. Kato</name><affiliation><mods:affiliation>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan</mods:affiliation></affiliation></author><author><name sortKey="Carroll, J" sort="Carroll, J" uniqKey="Carroll J" first="J" last="Carroll">J. Carroll</name><affiliation><mods:affiliation>Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia</mods:affiliation></affiliation></author><author><name sortKey="Lazaro, C" sort="Lazaro, C" uniqKey="Lazaro C" first="C" last="Lázaro">C. Lázaro</name><affiliation><mods:affiliation>Centre de Genètica Mèdica i Molecular – I.R.O., L’Hospitalet de Llobregat, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Joncourt, F" sort="Joncourt, F" uniqKey="Joncourt F" first="F" last="Joncourt">F. Joncourt</name><affiliation><mods:affiliation>Division of Human Genetics, Children’s University Hospital, Berne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Parry, D M" sort="Parry, D M" uniqKey="Parry D" first="D M" last="Parry">D M Parry</name><affiliation><mods:affiliation>Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA</mods:affiliation></affiliation></author><author><name sortKey="Rouleau, G A" sort="Rouleau, G A" uniqKey="Rouleau G" first="G A" last="Rouleau">G A Rouleau</name><affiliation><mods:affiliation>Department of Neurology, McGill University, Montreal, QC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Evans, D G R" sort="Evans, D G R" uniqKey="Evans D" first="D G R" last="Evans">D G R. Evans</name><affiliation><mods:affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</mods:affiliation></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="2005-07">2005-07</date><biblScope unit="volume">42</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="540">540</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>Amino</term><term>Amino terminal domain</term><term>Baser</term><term>Carboxy</term><term>Carboxy terminal domain</term><term>Covariates</term><term>Database</term><term>Deletion</term><term>Different regions</term><term>Equal groups</term><term>Exon</term><term>Exon number</term><term>Fewer meningiomas</term><term>Frameshift</term><term>Frameshift mutations</term><term>Friedman</term><term>Functional domains</term><term>Genet</term><term>Helical domain</term><term>Intracranial</term><term>Intracranial meningiomas</term><term>Intrafamilial</term><term>Kluwe</term><term>Kuramoto</term><term>Large deletions</term><term>Mautner</term><term>Meningioma</term><term>Merlin</term><term>Missense</term><term>Missense mutations</term><term>Molecular level</term><term>Mosaicism</term><term>Mutation</term><term>NF2</term><term>Nearest exon</term><term>Neurofibromatosis</term><term>Neurofibromatosis type</term><term>Nonsense mutations</term><term>Other covariates</term><term>Phenotype</term><term>Polyposis</term><term>Present study</term><term>Pulst</term><term>Ramsden</term><term>Reference group</term><term>Rouleau</term><term>Schwannomas</term><term>Severe disease</term><term>Single class</term><term>Somatic</term><term>Somatic mosaicism</term><term>Somatic mosaics</term><term>Splice</term><term>Splice site</term><term>Splice site mutations</term><term>Suppressor</term><term>Symptom</term><term>Tumour</term><term>Vestibular</term><term>genotype-phenotype correlation</term><term>neurofibromatosis 2</term><term>splice site mutation</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Amino</term><term>Amino terminal domain</term><term>Baser</term><term>Carboxy</term><term>Carboxy terminal domain</term><term>Covariates</term><term>Database</term><term>Deletion</term><term>Different regions</term><term>Equal groups</term><term>Exon</term><term>Exon number</term><term>Fewer meningiomas</term><term>Frameshift</term><term>Frameshift mutations</term><term>Friedman</term><term>Functional domains</term><term>Genet</term><term>Helical domain</term><term>Intracranial</term><term>Intracranial meningiomas</term><term>Intrafamilial</term><term>Kluwe</term><term>Kuramoto</term><term>Large deletions</term><term>Mautner</term><term>Meningioma</term><term>Merlin</term><term>Missense</term><term>Missense mutations</term><term>Molecular level</term><term>Mosaicism</term><term>Mutation</term><term>Nearest exon</term><term>Neurofibromatosis</term><term>Neurofibromatosis type</term><term>Nonsense mutations</term><term>Other covariates</term><term>Phenotype</term><term>Polyposis</term><term>Present study</term><term>Pulst</term><term>Ramsden</term><term>Reference group</term><term>Rouleau</term><term>Schwannomas</term><term>Severe disease</term><term>Single class</term><term>Somatic</term><term>Somatic mosaicism</term><term>Somatic mosaics</term><term>Splice</term><term>Splice site</term><term>Splice site mutations</term><term>Suppressor</term><term>Symptom</term><term>Tumour</term><term>Vestibular</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.</div></front></TEI><istex><corpusName>bmj</corpusName><keywords><teeft><json:string>mutation</json:string><json:string>exon</json:string><json:string>splice site mutations</json:string><json:string>meningioma</json:string><json:string>splice</json:string><json:string>neurofibromatosis</json:string><json:string>deletion</json:string><json:string>genet</json:string><json:string>missense</json:string><json:string>merlin</json:string><json:string>tumour</json:string><json:string>missense mutations</json:string><json:string>frameshift</json:string><json:string>large deletions</json:string><json:string>reference 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number</json:string><json:string>kuramoto</json:string><json:string>covariates</json:string><json:string>amino</json:string><json:string>other covariates</json:string><json:string>somatic mosaicism</json:string><json:string>present study</json:string><json:string>equal groups</json:string><json:string>carboxy terminal domain</json:string><json:string>fewer meningiomas</json:string><json:string>symptom</json:string><json:string>somatic</json:string><json:string>severe disease</json:string><json:string>nearest exon</json:string><json:string>nonsense mutations</json:string><json:string>single class</json:string><json:string>different regions</json:string><json:string>helical domain</json:string><json:string>molecular level</json:string><json:string>splice site</json:string><json:string>friedman</json:string></teeft></keywords><author><json:item><name>M E Baser</name><affiliations><json:string>10622 Kinnard Ave, #203, Los Angeles, CA, USA</json:string></affiliations></json:item><json:item><name>L Kuramoto</name><affiliations><json:string>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>R Woods</name><affiliations><json:string>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>H Joe</name><affiliations><json:string>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>J M Friedman</name><affiliations><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>A J Wallace</name><affiliations><json:string>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</json:string></affiliations></json:item><json:item><name>R T Ramsden</name><affiliations><json:string>Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK</json:string></affiliations></json:item><json:item><name>S Olschwang</name><affiliations><json:string>INSERM U434, Fondation Jean-Dausset-CEPH, Paris, France</json:string></affiliations></json:item><json:item><name>E Bijlsma</name><affiliations><json:string>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</json:string></affiliations></json:item><json:item><name>M Kalamarides</name><affiliations><json:string>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</json:string></affiliations></json:item><json:item><name>L Papi</name><affiliations><json:string>Department of Clinical Physiopathology, University of Florence, Florence, Italy</json:string></affiliations></json:item><json:item><name>R Kato</name><affiliations><json:string>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan</json:string></affiliations></json:item><json:item><name>J Carroll</name><affiliations><json:string>Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia</json:string></affiliations></json:item><json:item><name>C Lázaro</name><affiliations><json:string>Centre de Genètica Mèdica i Molecular – I.R.O., L’Hospitalet de Llobregat, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>F Joncourt</name><affiliations><json:string>Division of Human Genetics, Children’s University Hospital, Berne, Switzerland</json:string></affiliations></json:item><json:item><name>D M Parry</name><affiliations><json:string>Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA</json:string></affiliations></json:item><json:item><name>G A Rouleau</name><affiliations><json:string>Department of Neurology, McGill University, Montreal, QC, Canada</json:string></affiliations></json:item><json:item><name>D G R Evans</name><affiliations><json:string>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>genotype-phenotype correlation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurofibromatosis 2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NF2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>splice site mutation</value></json:item></subject><arkIstex>ark:/67375/NVC-QK4MNXNR-2</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>review-article</json:string></originalGenre><abstract>Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.</abstract><qualityIndicators><score>9.04</score><pdfWordCount>6289</pdfWordCount><pdfCharCount>39920</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>170</abstractWordCount><abstractCharCount>1111</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2</title><pmid><json:string>15994874</json:string></pmid><genre><json:string>review-article</json:string></genre><host><title>Journal of Medical Genetics</title><language><json:string>unknown</json:string></language><issn><json:string>0022-2593</json:string></issn><eissn><json:string>1468-6244</json:string></eissn><volume>42</volume><issue>7</issue><pages><first>540</first></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2005-07-01</json:string></date><geogName></geogName><orgName><json:string>University Hospital, Berne, Switzerland D M Parry, Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA G A Rouleau, Department of Neurology</json:string><json:string>Canada Supported</json:string><json:string>University Department of Medical Genetics, St Mary</json:string><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</json:string><json:string>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</json:string><json:string>Division of Human Genetics</json:string><json:string>Department of Statistics, University of British Columbia</json:string><json:string>Department of Clinical Physiopathology, University of Florence, Florence, Italy</json:string><json:string>FBT Foundation and US Army</json:string><json:string>Department of Statistics, University of British Columbia, Vancouver, BC, Canada J</json:string><json:string>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan J Carroll, Division of Molecular Pathology, Institute of Medical and Veterinary Science</json:string><json:string>United Kingdom NF</json:string><json:string>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</json:string><json:string>Ministerio de Educacio y Ciencia</json:string><json:string>Fondo</json:string></orgName><orgName_funder><json:string>Fondo</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Gutmann</json:string><json:string>The</json:string></persName><placeName><json:string>Paris</json:string><json:string>Australia</json:string><json:string>UK</json:string><json:string>Montreal</json:string><json:string>Los Angeles</json:string><json:string>USA</json:string><json:string>Manchester</json:string><json:string>Barcelona</json:string><json:string>Adelaide</json:string><json:string>CA</json:string><json:string>France</json:string><json:string>Spain</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Kluwe et al</json:string><json:string>Wellenreuther et al</json:string><json:string>Bruder et al</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/NVC-QK4MNXNR-2</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - genetics & heredity</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - genetics & heredity</json:string></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 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Genetics</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>2005</publicationDate><copyrightDate>2005</copyrightDate><doi><json:string>10.1136/jmg.2004.029504</json:string></doi><id>5548BF6B4BF8D456AABF42A94A5E2B61B7E26056</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">BMJ Publishing Group Ltd</publisher><availability><licence><p>Copyright 2005 Journal of Medical Genetics</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-7M42M2QJ-2">bmj</p></availability><date>2005-07-01</date></publicationStmt><notesStmt><note type="review-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-L5L7X3NF-P">review-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Correspondence to:
Dr Michael E Baser
10622 Kinnard Ave, #203, Los Angeles, CA 90024; michael.baser@verizon.net</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2</title><author xml:id="author-0000"><persName><forename type="first">M E</forename><surname>Baser</surname></persName><affiliation>10622 Kinnard Ave, #203, Los Angeles, CA, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">L</forename><surname>Kuramoto</surname></persName><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author xml:id="author-0002"><persName><forename type="first">R</forename><surname>Woods</surname></persName><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author xml:id="author-0003"><persName><forename type="first">H</forename><surname>Joe</surname></persName><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author xml:id="author-0004"><persName><forename type="first">J M</forename><surname>Friedman</surname></persName><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author xml:id="author-0005"><persName><forename type="first">A J</forename><surname>Wallace</surname></persName><affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</affiliation></author><author xml:id="author-0006"><persName><forename type="first">R T</forename><surname>Ramsden</surname></persName><affiliation>Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK</affiliation></author><author xml:id="author-0007"><persName><forename type="first">S</forename><surname>Olschwang</surname></persName><affiliation>INSERM U434, Fondation Jean-Dausset-CEPH, Paris, France</affiliation></author><author xml:id="author-0008"><persName><forename type="first">E</forename><surname>Bijlsma</surname></persName><affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</affiliation></author><author xml:id="author-0009"><persName><forename type="first">M</forename><surname>Kalamarides</surname></persName><affiliation>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</affiliation></author><author xml:id="author-0010"><persName><forename type="first">L</forename><surname>Papi</surname></persName><affiliation>Department of Clinical Physiopathology, University of Florence, Florence, Italy</affiliation></author><author xml:id="author-0011"><persName><forename type="first">R</forename><surname>Kato</surname></persName><affiliation>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan</affiliation></author><author xml:id="author-0012"><persName><forename type="first">J</forename><surname>Carroll</surname></persName><affiliation>Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia</affiliation></author><author xml:id="author-0013"><persName><forename type="first">C</forename><surname>Lázaro</surname></persName><affiliation>Centre de Genètica Mèdica i Molecular – I.R.O., L’Hospitalet de Llobregat, Barcelona, Spain</affiliation></author><author xml:id="author-0014"><persName><forename type="first">F</forename><surname>Joncourt</surname></persName><affiliation>Division of Human Genetics, Children’s University Hospital, Berne, Switzerland</affiliation></author><author xml:id="author-0015"><persName><forename type="first">D M</forename><surname>Parry</surname></persName><affiliation>Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA</affiliation></author><author xml:id="author-0016"><persName><forename type="first">G A</forename><surname>Rouleau</surname></persName><affiliation>Department of Neurology, McGill University, Montreal, QC, Canada</affiliation></author><author xml:id="author-0017"><persName><forename type="first">D G R</forename><surname>Evans</surname></persName><affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</affiliation></author><idno type="istex">5548BF6B4BF8D456AABF42A94A5E2B61B7E26056</idno><idno type="ark">ark:/67375/NVC-QK4MNXNR-2</idno><idno type="DOI">10.1136/jmg.2004.029504</idno><idno type="href">jmedgenet-42-540.pdf</idno><idno type="PMID">15994874</idno><idno type="local">0420540</idno></analytic><monogr><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="pISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><idno type="PublisherID-hwp">jmedgenet</idno><idno type="PublisherID-nlm-ta">J Med Genet</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2005-07"></date><biblScope unit="volume">42</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="540">540</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2005-07-01</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>KWD</head><item><term>genotype-phenotype correlation</term></item><item><term>neurofibromatosis 2</term></item><item><term>NF2</term></item><item><term>splice site mutation</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-07-01">Created</change><change when="2005-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="review-article"><front><journal-meta><journal-id journal-id-type="hwp">jmedgenet</journal-id><journal-id journal-id-type="nlm-ta">J Med Genet</journal-id><journal-title>Journal of Medical Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">J Med Genet</abbrev-journal-title><issn pub-type="ppub">0022-2593</issn><issn pub-type="epub">1468-6244</issn><publisher><publisher-name>BMJ Publishing Group Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">0420540</article-id><article-id pub-id-type="doi">10.1136/jmg.2004.029504</article-id><article-id pub-id-type="other">jmedgenet;42/7/540</article-id><article-id pub-id-type="pmid">15994874</article-id><article-id pub-id-type="other">540</article-id><article-id pub-id-type="other">jmg.2004.029504</article-id><article-categories><subj-group subj-group-type="heading"><subject content-type="original">Review</subject></subj-group></article-categories><title-group><article-title>The location of constitutional <italic>neurofibromatosis 2</italic> (<italic>NF2</italic>) splice site mutations is associated with the severity of NF2</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Baser</surname><given-names>M E</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Kuramoto</surname><given-names>L</given-names></name><xref rid="AFF2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Woods</surname><given-names>R</given-names></name><xref rid="AFF2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Joe</surname><given-names>H</given-names></name><xref rid="AFF2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Friedman</surname><given-names>J M</given-names></name><xref rid="AFF3">3</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wallace</surname><given-names>A J</given-names></name><xref rid="AFF4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ramsden</surname><given-names>R T</given-names></name><xref rid="AFF5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Olschwang</surname><given-names>S</given-names></name><xref rid="AFF6">6</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bijlsma</surname><given-names>E</given-names></name><xref rid="AFF7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Kalamarides</surname><given-names>M</given-names></name><xref rid="AFF8">8</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Papi</surname><given-names>L</given-names></name><xref rid="AFF9">9</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Kato</surname><given-names>R</given-names></name><xref rid="AFF10">10</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Carroll</surname><given-names>J</given-names></name><xref rid="AFF11">11</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lázaro</surname><given-names>C</given-names></name><xref rid="AFF12">12</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Joncourt</surname><given-names>F</given-names></name><xref rid="AFF13">13</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Parry</surname><given-names>D M</given-names></name><xref rid="AFF14">14</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Rouleau</surname><given-names>G A</given-names></name><xref rid="AFF15">15</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Evans</surname><given-names>D G R</given-names></name><xref rid="AFF4">4</xref></contrib><aff id="AFF1"><label>1</label>10622 Kinnard Ave, #203, Los Angeles, CA, USA</aff><aff id="AFF2"><label>2</label>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</aff><aff id="AFF3"><label>3</label>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</aff><aff id="AFF4"><label>4</label>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</aff><aff id="AFF5"><label>5</label>Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK</aff><aff id="AFF6"><label>6</label>INSERM U434, Fondation Jean-Dausset-CEPH, Paris, France</aff><aff id="AFF7"><label>7</label>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="AFF8"><label>8</label>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</aff><aff id="AFF9"><label>9</label>Department of Clinical Physiopathology, University of Florence, Florence, Italy</aff><aff id="AFF10"><label>10</label>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan</aff><aff id="AFF11"><label>11</label>Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia</aff><aff id="AFF12"><label>12</label>Centre de Genètica Mèdica i Molecular – I.R.O., L’Hospitalet de Llobregat, Barcelona, Spain</aff><aff id="AFF13"><label>13</label>Division of Human Genetics, Children’s University Hospital, Berne, Switzerland</aff><aff id="AFF14"><label>14</label>Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA</aff><aff id="AFF15"><label>15</label>Department of Neurology, McGill University, Montreal, QC, Canada</aff></contrib-group><author-notes><corresp>Correspondence to:
Dr Michael E Baser
10622 Kinnard Ave, #203, Los Angeles, CA 90024; <ext-link xlink:href="michael.baserverizon.net" ext-link-type="email" xlink:type="simple">michael.baser@verizon.net</ext-link></corresp></author-notes><pub-date pub-type="ppub"><month>7</month><year>2005</year></pub-date><pub-date pub-type="epub"><day>1</day><month>7</month><year>2005</year></pub-date><volume>42</volume><volume-id pub-id-type="other">42</volume-id><volume-id pub-id-type="other">42</volume-id><issue>7</issue><issue-id pub-id-type="other">jmedgenet;42/7</issue-id><issue-id pub-id-type="other">7</issue-id><issue-id pub-id-type="other">42/7</issue-id><fpage>540</fpage><history><date date-type="accepted"><day>15</day><month>12</month><year>2004</year></date><date date-type="rev-recd"><day>14</day><month>12</month><year>2004</year></date></history><permissions><copyright-statement>Copyright 2005 Journal of Medical Genetics</copyright-statement><copyright-year>2005</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-42-540.pdf"></self-uri><abstract xml:lang="en"><p>Neurofibromatosis 2 (NF2) patients with constitutional splice site <italic>NF2</italic> mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional <italic>NF2</italic> mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.</p></abstract><kwd-group kwd-group-type="KWD" xml:lang="en"><kwd>genotype-phenotype correlation</kwd><kwd>neurofibromatosis 2</kwd><kwd>NF2</kwd><kwd>splice site mutation</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2</title></titleInfo><name type="personal"><namePart type="given">M E</namePart><namePart type="family">Baser</namePart><affiliation>10622 Kinnard Ave, #203, Los Angeles, CA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Kuramoto</namePart><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Woods</namePart><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H</namePart><namePart type="family">Joe</namePart><affiliation>Department of Statistics, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J M</namePart><namePart type="family">Friedman</namePart><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A J</namePart><namePart type="family">Wallace</namePart><affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R T</namePart><namePart type="family">Ramsden</namePart><affiliation>Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Olschwang</namePart><affiliation>INSERM U434, Fondation Jean-Dausset-CEPH, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Bijlsma</namePart><affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Kalamarides</namePart><affiliation>Department of Neurosurgery, University Hospital Beaujon, Clichy, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Papi</namePart><affiliation>Department of Clinical Physiopathology, University of Florence, Florence, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Kato</namePart><affiliation>Department of Pediatrics, Higashisaitama National Hospital, Saitama, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Carroll</namePart><affiliation>Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Lázaro</namePart><affiliation>Centre de Genètica Mèdica i Molecular – I.R.O., L’Hospitalet de Llobregat, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F</namePart><namePart type="family">Joncourt</namePart><affiliation>Division of Human Genetics, Children’s University Hospital, Berne, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D M</namePart><namePart type="family">Parry</namePart><affiliation>Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G A</namePart><namePart type="family">Rouleau</namePart><affiliation>Department of Neurology, McGill University, Montreal, QC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D G R</namePart><namePart type="family">Evans</namePart><affiliation>University Department of Medical Genetics, St Mary’s Hospital, Manchester, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="review-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-L5L7X3NF-P">review-article</genre><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2005-07</dateIssued><dateCreated encoding="w3cdtf">2005-07-01</dateCreated><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.</abstract><note type="author-notes">Correspondence to:
Dr Michael E Baser
10622 Kinnard Ave, #203, Los Angeles, CA 90024; michael.baser@verizon.net</note><subject lang="en"><genre>KWD</genre><topic>genotype-phenotype correlation</topic><topic>neurofibromatosis 2</topic><topic>NF2</topic><topic>splice site mutation</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title></titleInfo><titleInfo type="abbreviated"><title>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><identifier type="ISSN">0022-2593</identifier><identifier type="eISSN">1468-6244</identifier><identifier type="PublisherID-hwp">jmedgenet</identifier><identifier type="PublisherID-nlm-ta">J Med Genet</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>42</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>540</start></extent></part></relatedItem><identifier type="istex">5548BF6B4BF8D456AABF42A94A5E2B61B7E26056</identifier><identifier type="ark">ark:/67375/NVC-QK4MNXNR-2</identifier><identifier type="DOI">10.1136/jmg.2004.029504</identifier><identifier type="href">jmedgenet-42-540.pdf</identifier><identifier type="PMID">15994874</identifier><identifier type="local">0420540</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright 2005 Journal of Medical Genetics</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-7M42M2QJ-2">bmj</recordContentSource><recordOrigin>Copyright 2005 Journal of Medical Genetics</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/metadata/json</uri></json:item></metadata><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/5548BF6B4BF8D456AABF42A94A5E2B61B7E26056/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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