20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits
Identifieur interne : 001445 ( Main/Corpus ); précédent : 001444; suivant : 00144620p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits
Auteurs : S R Lalani ; J V Thakuria ; G F Cox ; X. Wang ; W. Bi ; M S Bray ; C. Shaw ; S W Cheung ; A C Chinault ; B A Boggs ; Z. Ou ; E K Brundage ; J R Lupski ; J. Gentile ; S. Waisbren ; A. Pursley ; L. Ma ; M. Khajavi ; G. Zapata ; R. Friedman ; J J Kim ; J A Towbin ; P. Stankiewicz ; S. Schnittger ; I. Hansmann ; T. Ai ; S. Sood ; X H Wehrens ; J F Martin ; J W Belmont ; L. PotockiSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2009-03.
Abstract
Background: Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. Methods and results: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.
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DOI: 10.1136/jmg.2008.061002
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title><author><name sortKey="Lalani, S R" sort="Lalani, S R" uniqKey="Lalani S" first="S R" last="Lalani">S R Lalani</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Thakuria, J V" sort="Thakuria, J V" uniqKey="Thakuria J" first="J V" last="Thakuria">J V Thakuria</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Cox, G F" sort="Cox, G F" uniqKey="Cox G" first="G F" last="Cox">G F Cox</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Wang, X" sort="Wang, X" uniqKey="Wang X" first="X" last="Wang">X. Wang</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Bi, W" sort="Bi, W" uniqKey="Bi W" first="W" last="Bi">W. Bi</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Bray, M S" sort="Bray, M S" uniqKey="Bray M" first="M S" last="Bray">M S Bray</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Shaw, C" sort="Shaw, C" uniqKey="Shaw C" first="C" last="Shaw">C. Shaw</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Cheung, S W" sort="Cheung, S W" uniqKey="Cheung S" first="S W" last="Cheung">S W Cheung</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Chinault, A C" sort="Chinault, A C" uniqKey="Chinault A" first="A C" last="Chinault">A C Chinault</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Boggs, B A" sort="Boggs, B A" uniqKey="Boggs B" first="B A" last="Boggs">B A Boggs</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Ou, Z" sort="Ou, Z" uniqKey="Ou Z" first="Z" last="Ou">Z. Ou</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Brundage, E K" sort="Brundage, E K" uniqKey="Brundage E" first="E K" last="Brundage">E K Brundage</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Lupski, J R" sort="Lupski, J R" uniqKey="Lupski J" first="J R" last="Lupski">J R Lupski</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Gentile, J" sort="Gentile, J" uniqKey="Gentile J" first="J" last="Gentile">J. Gentile</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Waisbren, S" sort="Waisbren, S" uniqKey="Waisbren S" first="S" last="Waisbren">S. Waisbren</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Pursley, A" sort="Pursley, A" uniqKey="Pursley A" first="A" last="Pursley">A. Pursley</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Ma, L" sort="Ma, L" uniqKey="Ma L" first="L" last="Ma">L. Ma</name><affiliation><mods:affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Khajavi, M" sort="Khajavi, M" uniqKey="Khajavi M" first="M" last="Khajavi">M. Khajavi</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Zapata, G" sort="Zapata, G" uniqKey="Zapata G" first="G" last="Zapata">G. Zapata</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Friedman, R" sort="Friedman, R" uniqKey="Friedman R" first="R" last="Friedman">R. Friedman</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Kim, J J" sort="Kim, J J" uniqKey="Kim J" first="J J" last="Kim">J J Kim</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Towbin, J A" sort="Towbin, J A" uniqKey="Towbin J" first="J A" last="Towbin">J A Towbin</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Stankiewicz, P" sort="Stankiewicz, P" uniqKey="Stankiewicz P" first="P" last="Stankiewicz">P. Stankiewicz</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Schnittger, S" sort="Schnittger, S" uniqKey="Schnittger S" first="S" last="Schnittger">S. Schnittger</name><affiliation><mods:affiliation>MLL Munich Leukemia Laboratory, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hansmann, I" sort="Hansmann, I" uniqKey="Hansmann I" first="I" last="Hansmann">I. Hansmann</name><affiliation><mods:affiliation>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ai, T" sort="Ai, T" uniqKey="Ai T" first="T" last="Ai">T. Ai</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Sood, S" sort="Sood, S" uniqKey="Sood S" first="S" last="Sood">S. Sood</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Wehrens, X H" sort="Wehrens, X H" uniqKey="Wehrens X" first="X H" last="Wehrens">X H Wehrens</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Martin, J F" sort="Martin, J F" uniqKey="Martin J" first="J F" last="Martin">J F Martin</name><affiliation><mods:affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Belmont, J W" sort="Belmont, J W" uniqKey="Belmont J" first="J W" last="Belmont">J W Belmont</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Potocki, L" sort="Potocki, L" uniqKey="Potocki L" first="L" last="Potocki">L. Potocki</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:83785B14EAA8E305BD4E5BA4878032A7DE719691</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1136/jmg.2008.061002</idno><idno type="url">https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001445</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title><author><name sortKey="Lalani, S R" sort="Lalani, S R" uniqKey="Lalani S" first="S R" last="Lalani">S R Lalani</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Thakuria, J V" sort="Thakuria, J V" uniqKey="Thakuria J" first="J V" last="Thakuria">J V Thakuria</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Cox, G F" sort="Cox, G F" uniqKey="Cox G" first="G F" last="Cox">G F Cox</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Wang, X" sort="Wang, X" uniqKey="Wang X" first="X" last="Wang">X. Wang</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Bi, W" sort="Bi, W" uniqKey="Bi W" first="W" last="Bi">W. Bi</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Bray, M S" sort="Bray, M S" uniqKey="Bray M" first="M S" last="Bray">M S Bray</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Shaw, C" sort="Shaw, C" uniqKey="Shaw C" first="C" last="Shaw">C. Shaw</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Cheung, S W" sort="Cheung, S W" uniqKey="Cheung S" first="S W" last="Cheung">S W Cheung</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Chinault, A C" sort="Chinault, A C" uniqKey="Chinault A" first="A C" last="Chinault">A C Chinault</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Boggs, B A" sort="Boggs, B A" uniqKey="Boggs B" first="B A" last="Boggs">B A Boggs</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Ou, Z" sort="Ou, Z" uniqKey="Ou Z" first="Z" last="Ou">Z. Ou</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Brundage, E K" sort="Brundage, E K" uniqKey="Brundage E" first="E K" last="Brundage">E K Brundage</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Lupski, J R" sort="Lupski, J R" uniqKey="Lupski J" first="J R" last="Lupski">J R Lupski</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Gentile, J" sort="Gentile, J" uniqKey="Gentile J" first="J" last="Gentile">J. Gentile</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Waisbren, S" sort="Waisbren, S" uniqKey="Waisbren S" first="S" last="Waisbren">S. Waisbren</name><affiliation><mods:affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</mods:affiliation></affiliation></author><author><name sortKey="Pursley, A" sort="Pursley, A" uniqKey="Pursley A" first="A" last="Pursley">A. Pursley</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Ma, L" sort="Ma, L" uniqKey="Ma L" first="L" last="Ma">L. Ma</name><affiliation><mods:affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Khajavi, M" sort="Khajavi, M" uniqKey="Khajavi M" first="M" last="Khajavi">M. Khajavi</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Zapata, G" sort="Zapata, G" uniqKey="Zapata G" first="G" last="Zapata">G. Zapata</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Friedman, R" sort="Friedman, R" uniqKey="Friedman R" first="R" last="Friedman">R. Friedman</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Kim, J J" sort="Kim, J J" uniqKey="Kim J" first="J J" last="Kim">J J Kim</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Towbin, J A" sort="Towbin, J A" uniqKey="Towbin J" first="J A" last="Towbin">J A Towbin</name><affiliation><mods:affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Stankiewicz, P" sort="Stankiewicz, P" uniqKey="Stankiewicz P" first="P" last="Stankiewicz">P. Stankiewicz</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Schnittger, S" sort="Schnittger, S" uniqKey="Schnittger S" first="S" last="Schnittger">S. Schnittger</name><affiliation><mods:affiliation>MLL Munich Leukemia Laboratory, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hansmann, I" sort="Hansmann, I" uniqKey="Hansmann I" first="I" last="Hansmann">I. Hansmann</name><affiliation><mods:affiliation>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ai, T" sort="Ai, T" uniqKey="Ai T" first="T" last="Ai">T. Ai</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Sood, S" sort="Sood, S" uniqKey="Sood S" first="S" last="Sood">S. Sood</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Wehrens, X H" sort="Wehrens, X H" uniqKey="Wehrens X" first="X H" last="Wehrens">X H Wehrens</name><affiliation><mods:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Martin, J F" sort="Martin, J F" uniqKey="Martin J" first="J F" last="Martin">J F Martin</name><affiliation><mods:affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Belmont, J W" sort="Belmont, J W" uniqKey="Belmont J" first="J W" last="Belmont">J W Belmont</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Potocki, L" sort="Potocki, L" uniqKey="Potocki L" first="L" last="Potocki">L. Potocki</name><affiliation><mods:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</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="2009-03">2009-03</date><biblScope unit="volume">46</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="168">168</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">83785B14EAA8E305BD4E5BA4878032A7DE719691</idno><idno type="DOI">10.1136/jmg.2008.061002</idno><idno type="href">jmedgenet-46-168.pdf</idno><idno type="ArticleID">mg61002</idno><idno type="PMID">18812404</idno><idno type="local">jmedgenet;46/3/168</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background: Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. Methods and results: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>S R Lalani</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J V Thakuria</name><affiliations><json:string>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</json:string></affiliations></json:item><json:item><name>G F Cox</name><affiliations><json:string>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</json:string></affiliations></json:item><json:item><name>X Wang</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>W Bi</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>M S Bray</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>C Shaw</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>S W Cheung</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>A C Chinault</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>B A Boggs</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>Z Ou</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>E K Brundage</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J R Lupski</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J Gentile</name><affiliations><json:string>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</json:string></affiliations></json:item><json:item><name>S Waisbren</name><affiliations><json:string>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</json:string></affiliations></json:item><json:item><name>A Pursley</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>L Ma</name><affiliations><json:string>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>M Khajavi</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>G Zapata</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>R Friedman</name><affiliations><json:string>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J J Kim</name><affiliations><json:string>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J A Towbin</name><affiliations><json:string>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>P Stankiewicz</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>S Schnittger</name><affiliations><json:string>MLL Munich Leukemia Laboratory, Munich, Germany</json:string></affiliations></json:item><json:item><name>I Hansmann</name><affiliations><json:string>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</json:string></affiliations></json:item><json:item><name>T Ai</name><affiliations><json:string>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>S Sood</name><affiliations><json:string>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>X H Wehrens</name><affiliations><json:string>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J F Martin</name><affiliations><json:string>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>J W Belmont</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>L Potocki</name><affiliations><json:string>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original articles</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Liver disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cardiomyopathy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Pancreas and biliary tract</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Arrhythmias</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Background: Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. Methods and results: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.</abstract><qualityIndicators><score>7.384</score><pdfVersion>1.2</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1480</abstractCharCount><pdfWordCount>4792</pdfWordCount><pdfCharCount>31352</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>216</abstractWordCount></qualityIndicators><title>20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title><pmid><json:string>18812404</json:string></pmid><genre><json:string>research-article</json:string></genre><host><volume>46</volume><pages><first>168</first></pages><issn><json:string>0022-2593</json:string></issn><issue>3</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-6244</json:string></eissn><title>Journal of Medical Genetics</title></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1136/jmg.2008.061002</json:string></doi><id>83785B14EAA8E305BD4E5BA4878032A7DE719691</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd</publisher><availability><p>BMJ</p></availability><date>2008-09-23</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title><author><persName><forename type="first">S R</forename><surname>Lalani</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J V</forename><surname>Thakuria</surname></persName><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation></author><author><persName><forename type="first">G F</forename><surname>Cox</surname></persName><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation></author><author><persName><forename type="first">X</forename><surname>Wang</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">W</forename><surname>Bi</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">M S</forename><surname>Bray</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">C</forename><surname>Shaw</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">S W</forename><surname>Cheung</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">A C</forename><surname>Chinault</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">B A</forename><surname>Boggs</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">Z</forename><surname>Ou</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">E K</forename><surname>Brundage</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J R</forename><surname>Lupski</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J</forename><surname>Gentile</surname></persName><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation></author><author><persName><forename type="first">S</forename><surname>Waisbren</surname></persName><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation></author><author><persName><forename type="first">A</forename><surname>Pursley</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">L</forename><surname>Ma</surname></persName><affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">M</forename><surname>Khajavi</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">G</forename><surname>Zapata</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">R</forename><surname>Friedman</surname></persName><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J J</forename><surname>Kim</surname></persName><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J A</forename><surname>Towbin</surname></persName><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">P</forename><surname>Stankiewicz</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">S</forename><surname>Schnittger</surname></persName><affiliation>MLL Munich Leukemia Laboratory, Munich, Germany</affiliation></author><author><persName><forename type="first">I</forename><surname>Hansmann</surname></persName><affiliation>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</affiliation></author><author><persName><forename type="first">T</forename><surname>Ai</surname></persName><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">S</forename><surname>Sood</surname></persName><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">X H</forename><surname>Wehrens</surname></persName><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J F</forename><surname>Martin</surname></persName><affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">J W</forename><surname>Belmont</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">L</forename><surname>Potocki</surname></persName><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation></author></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><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-03"></date><biblScope unit="volume">46</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="168">168</biblScope></imprint></monogr><idno type="istex">83785B14EAA8E305BD4E5BA4878032A7DE719691</idno><idno type="DOI">10.1136/jmg.2008.061002</idno><idno type="href">jmedgenet-46-168.pdf</idno><idno type="ArticleID">mg61002</idno><idno type="PMID">18812404</idno><idno type="local">jmedgenet;46/3/168</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008-09-23</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Background: Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. Methods and results: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.</p></abstract><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Liver disease</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Cardiomyopathy</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Pancreas and biliary tract</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Arrhythmias</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-09-23">Created</change><change when="2009-03">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/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 article-type="research-article" xml:lang="EN"><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-id journal-id-type="publisher-id">jmg</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="publisher-id">mg61002</article-id><article-id pub-id-type="doi">10.1136/jmg.2008.061002</article-id><article-id pub-id-type="other">jmedgenet;46/3/168</article-id><article-id pub-id-type="other">jmedgenet;jmg.2008.061002</article-id><article-id pub-id-type="pmid">18812404</article-id><article-id pub-id-type="other">168</article-id><article-id pub-id-type="other">jmg.2008.061002</article-id><article-categories><subj-group subj-group-type="heading"><subject content-type="original">Original articles</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Liver disease</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Cardiomyopathy</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Pancreas and biliary tract</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Arrhythmias</subject></subj-group></article-categories><title-group><article-title>20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</article-title><alt-title alt-title-type="running-head">Original article</alt-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lalani</surname><given-names>S R</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Thakuria</surname><given-names>J V</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cox</surname><given-names>G F</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wang</surname><given-names>X</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bi</surname><given-names>W</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bray</surname><given-names>M S</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Shaw</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cheung</surname><given-names>S W</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Chinault</surname><given-names>A C</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Boggs</surname><given-names>B A</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ou</surname><given-names>Z</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Brundage</surname><given-names>E K</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lupski</surname><given-names>J R</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gentile</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Waisbren</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Pursley</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ma</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Khajavi</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Zapata</surname><given-names>G</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Friedman</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Kim</surname><given-names>J J</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Towbin</surname><given-names>J A</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Stankiewicz</surname><given-names>P</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Schnittger</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Hansmann</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ai</surname><given-names>T</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Sood</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wehrens</surname><given-names>X H</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Martin</surname><given-names>J F</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Belmont</surname><given-names>J W</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Potocki</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</addr-line> </aff><aff id="aff2"><label>2</label><addr-line>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</addr-line> </aff><aff id="aff3"><label>3</label><addr-line>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</addr-line> </aff><aff id="aff4"><label>4</label><addr-line>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</addr-line> </aff><aff id="aff5"><label>5</label><addr-line>MLL Munich Leukemia Laboratory, Munich, Germany</addr-line> </aff><aff id="aff6"><label>6</label><addr-line>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</addr-line> </aff><aff id="aff7"><label>7</label><addr-line>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</addr-line> </aff><author-notes><corresp>Dr S R Lalani, Department of Molecular and Human Genetics, One Baylor Plaza, BCM225, MARB, R713, Houston, Texas 77030, USA; <email xlink:type="simple">seemal@bcm.tmc.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>3</month><year>2009</year></pub-date><pub-date pub-type="epub-original"><day>26</day><month>11</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>23</day><month>9</month><year>2008</year></pub-date><volume>46</volume><volume-id pub-id-type="other">46</volume-id><volume-id pub-id-type="other">46</volume-id><issue>3</issue><issue-id pub-id-type="other">jmedgenet;46/3</issue-id><issue-id pub-id-type="other">3</issue-id><issue-id pub-id-type="other">46/3</issue-id><fpage>168</fpage><history><date date-type="received"><day>11</day><month>6</month><year>2008</year></date><date date-type="rev-recd"><day>14</day><month>8</month><year>2008</year></date><date date-type="accepted"><day>26</day><month>8</month><year>2008</year></date></history><permissions><copyright-statement>2009 BMJ Publishing Group Ltd</copyright-statement><copyright-year>2009</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-46-168.pdf"></self-uri><abstract><sec><title>Background:</title><p>Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in <italic>PRKAG2</italic> have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation.</p></sec><sec><title>Methods and results:</title><p>Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, <italic>BMP2</italic>. In two individuals with additional features of Alagille syndrome, deletion of both <italic>JAG1</italic> and <italic>BMP2</italic> were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory.</p></sec><sec><title>Conclusions:</title><p>Our findings demonstrate a novel genomic disorder characterised by deletion of <italic>BMP2</italic> with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.</p></sec></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>20p12.3 microdeletion predisposes to Wolff–Parkinson–White syndrome with variable neurocognitive deficits</title></titleInfo><name type="personal"><namePart type="given">S R</namePart><namePart type="family">Lalani</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J V</namePart><namePart type="family">Thakuria</namePart><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G F</namePart><namePart type="family">Cox</namePart><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">X</namePart><namePart type="family">Wang</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">W</namePart><namePart type="family">Bi</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M S</namePart><namePart type="family">Bray</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Shaw</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S W</namePart><namePart type="family">Cheung</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A C</namePart><namePart type="family">Chinault</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B A</namePart><namePart type="family">Boggs</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Z</namePart><namePart type="family">Ou</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E K</namePart><namePart type="family">Brundage</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J R</namePart><namePart type="family">Lupski</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Gentile</namePart><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Waisbren</namePart><affiliation>Division of Genetics, Children’s Hospital Boston, Boston, Massachusetts, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Pursley</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Ma</namePart><affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Khajavi</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">Zapata</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Friedman</namePart><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J J</namePart><namePart type="family">Kim</namePart><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J A</namePart><namePart type="family">Towbin</namePart><affiliation>Department of Cardiology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Stankiewicz</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Schnittger</namePart><affiliation>MLL Munich Leukemia Laboratory, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">I</namePart><namePart type="family">Hansmann</namePart><affiliation>Institut für Humangenetik und Medizinische Biologie, Halle/Saale, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">T</namePart><namePart type="family">Ai</namePart><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Sood</namePart><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">X H</namePart><namePart type="family">Wehrens</namePart><affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J F</namePart><namePart type="family">Martin</namePart><affiliation>Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J W</namePart><namePart type="family">Belmont</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Potocki</namePart><affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><genre>hwp-journal-coll</genre><topic>Liver disease</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Cardiomyopathy</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Pancreas and biliary tract</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Arrhythmias</topic></subject><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2009-03</dateIssued><dateCreated encoding="w3cdtf">2008-09-23</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Background: Wolff–Parkinson–White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. Methods and results: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. Conclusions: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.</abstract><relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title></titleInfo><titleInfo type="abbreviated"><title>J Med Genet</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0022-2593</identifier><identifier type="eISSN">1468-6244</identifier><identifier type="PublisherID">jmg</identifier><identifier type="PublisherID-hwp">jmedgenet</identifier><identifier type="PublisherID-nlm-ta">J Med Genet</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>46</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>168</start></extent></part></relatedItem><identifier type="istex">83785B14EAA8E305BD4E5BA4878032A7DE719691</identifier><identifier type="DOI">10.1136/jmg.2008.061002</identifier><identifier type="href">jmedgenet-46-168.pdf</identifier><identifier type="ArticleID">mg61002</identifier><identifier type="PMID">18812404</identifier><identifier type="local">jmedgenet;46/3/168</identifier><accessCondition type="use and reproduction" contentType="copyright">2009 BMJ Publishing Group Ltd</accessCondition><recordInfo><recordContentSource>BMJ</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/83785B14EAA8E305BD4E5BA4878032A7DE719691/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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