Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly
BACKGROUND—Ebstein anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding β-m...
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creator | Postma, Alex V van Engelen, Klaartje van de Meerakker, Judith Rahman, Thahira Probst, Susanne Baars, Marieke J.H Bauer, Ulrike Pickardt, Thomas Sperling, Silke R Berger, Felix Moorman, Antoon F.M Mulder, Barbara J.M Thierfelder, Ludwig Keavney, Bernard Goodship, Judith Klaassen, Sabine |
description | BACKGROUND—Ebstein anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding β-myosin heavy chain has been shown; in this report, we have screened for MYH7 mutations in a cohort of probands with Ebstein anomaly in a large population-based study.
METHODS AND RESULTS—Mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly was performed by next-generation sequencing and direct DNA sequencing of MYH7. Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found; 5 were novel and 2 were known to cause hypertrophic cardiomyopathy. All mutations except for 1 3-bp deletion were missense mutations; 1 was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein anomaly (P |
doi_str_mv | 10.1161/CIRCGENETICS.110.957985 |
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METHODS AND RESULTS—Mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly was performed by next-generation sequencing and direct DNA sequencing of MYH7. Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found; 5 were novel and 2 were known to cause hypertrophic cardiomyopathy. All mutations except for 1 3-bp deletion were missense mutations; 1 was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein anomaly (P<0.0001). LVNC segregated with the MYH7 mutation in the pedigrees of 3 of the probands, 1 of which also included another individual with Ebstein anomaly.
CONCLUSIONS—Ebstein anomaly is a congenital heart malformation that is associated with mutations in MYH7. MYH7 mutations are predominantly found in Ebstein anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.</description><identifier>ISSN: 1942-325X</identifier><identifier>ISSN: 1942-3268</identifier><identifier>EISSN: 1942-3268</identifier><identifier>DOI: 10.1161/CIRCGENETICS.110.957985</identifier><identifier>PMID: 21127202</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Biological and medical sciences ; Cardiac Myosins - chemistry ; Cardiac Myosins - genetics ; Cardiology. Vascular system ; Child ; Child, Preschool ; Cohort Studies ; Ebstein Anomaly - diagnostic imaging ; Ebstein Anomaly - genetics ; Family ; Female ; General aspects. Genetic counseling ; Heart ; Humans ; Infant ; Male ; Medical genetics ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; Mutation - genetics ; Myocarditis. Cardiomyopathies ; Myosin Heavy Chains - chemistry ; Myosin Heavy Chains - genetics ; Pedigree ; Sarcomeres - genetics ; Ultrasonography ; Young Adult</subject><ispartof>Circulation. Cardiovascular genetics, 2011-02, Vol.4 (1), p.43-50</ispartof><rights>2011 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4699-491dbabec07a85e09de67f9bf24fbc35f4d6df832098f2a4e1f3a1343da415d43</citedby><cites>FETCH-LOGICAL-c4699-491dbabec07a85e09de67f9bf24fbc35f4d6df832098f2a4e1f3a1343da415d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23866480$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21127202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Postma, Alex V</creatorcontrib><creatorcontrib>van Engelen, Klaartje</creatorcontrib><creatorcontrib>van de Meerakker, Judith</creatorcontrib><creatorcontrib>Rahman, Thahira</creatorcontrib><creatorcontrib>Probst, Susanne</creatorcontrib><creatorcontrib>Baars, Marieke J.H</creatorcontrib><creatorcontrib>Bauer, Ulrike</creatorcontrib><creatorcontrib>Pickardt, Thomas</creatorcontrib><creatorcontrib>Sperling, Silke R</creatorcontrib><creatorcontrib>Berger, Felix</creatorcontrib><creatorcontrib>Moorman, Antoon F.M</creatorcontrib><creatorcontrib>Mulder, Barbara J.M</creatorcontrib><creatorcontrib>Thierfelder, Ludwig</creatorcontrib><creatorcontrib>Keavney, Bernard</creatorcontrib><creatorcontrib>Goodship, Judith</creatorcontrib><creatorcontrib>Klaassen, Sabine</creatorcontrib><title>Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly</title><title>Circulation. Cardiovascular genetics</title><addtitle>Circ Cardiovasc Genet</addtitle><description>BACKGROUND—Ebstein anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding β-myosin heavy chain has been shown; in this report, we have screened for MYH7 mutations in a cohort of probands with Ebstein anomaly in a large population-based study.
METHODS AND RESULTS—Mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly was performed by next-generation sequencing and direct DNA sequencing of MYH7. Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found; 5 were novel and 2 were known to cause hypertrophic cardiomyopathy. All mutations except for 1 3-bp deletion were missense mutations; 1 was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein anomaly (P<0.0001). LVNC segregated with the MYH7 mutation in the pedigrees of 3 of the probands, 1 of which also included another individual with Ebstein anomaly.
CONCLUSIONS—Ebstein anomaly is a congenital heart malformation that is associated with mutations in MYH7. MYH7 mutations are predominantly found in Ebstein anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Cardiac Myosins - chemistry</subject><subject>Cardiac Myosins - genetics</subject><subject>Cardiology. Vascular system</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Ebstein Anomaly - diagnostic imaging</subject><subject>Ebstein Anomaly - genetics</subject><subject>Family</subject><subject>Female</subject><subject>General aspects. Genetic counseling</subject><subject>Heart</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation - genetics</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myosin Heavy Chains - chemistry</subject><subject>Myosin Heavy Chains - genetics</subject><subject>Pedigree</subject><subject>Sarcomeres - genetics</subject><subject>Ultrasonography</subject><subject>Young Adult</subject><issn>1942-325X</issn><issn>1942-3268</issn><issn>1942-3268</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90Etr3DAQB3ARGppXv0LqS2kuTjSSrMcxmO1mIWkhD0hOQrZHrFs_Uskm5NtXYTePUw9ixOg3GvgT8hXoKYCEs3J1XS4XPxe3q_ImdeipKZTRxQ7ZByNYzpnUn97uxf0eOYjxN6VScC4_kz0GwBSjbJ-oq3lyUzsOMWuHbFpjduNCPfYYMFvigNnVw4V6eVpUccJUz4exd93zEdn1rov4ZVsPyd2PxW15kV_-Wq7K88u8FtKYXBhoKldhTZXTBVLToFTeVJ4JX9W88KKRjdecUaM9cwLBcwdc8MYJKBrBD8n3zb-PYfw7Y5xs38Yau84NOM7R6kIDFEypJE_-K0EKJkFwxhJVG1qHMcaA3j6Gtnfh2QK1L_naj_mmDrWbfNPk8XbJXPXYvM29BprAty1wsXadD26o2_juuJZSaJqc2LinsZswxD_d_ITBrtF109pS4FwJo3JG03JGKc3ToYb_A7Fckhg</recordid><startdate>201102</startdate><enddate>201102</enddate><creator>Postma, Alex V</creator><creator>van Engelen, Klaartje</creator><creator>van de Meerakker, Judith</creator><creator>Rahman, Thahira</creator><creator>Probst, Susanne</creator><creator>Baars, Marieke J.H</creator><creator>Bauer, Ulrike</creator><creator>Pickardt, Thomas</creator><creator>Sperling, Silke R</creator><creator>Berger, Felix</creator><creator>Moorman, Antoon F.M</creator><creator>Mulder, Barbara J.M</creator><creator>Thierfelder, Ludwig</creator><creator>Keavney, Bernard</creator><creator>Goodship, Judith</creator><creator>Klaassen, Sabine</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201102</creationdate><title>Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly</title><author>Postma, Alex V ; van Engelen, Klaartje ; van de Meerakker, Judith ; Rahman, Thahira ; Probst, Susanne ; Baars, Marieke J.H ; Bauer, Ulrike ; Pickardt, Thomas ; Sperling, Silke R ; Berger, Felix ; Moorman, Antoon F.M ; Mulder, Barbara J.M ; Thierfelder, Ludwig ; Keavney, Bernard ; Goodship, Judith ; Klaassen, Sabine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4699-491dbabec07a85e09de67f9bf24fbc35f4d6df832098f2a4e1f3a1343da415d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>Cardiac Myosins - chemistry</topic><topic>Cardiac Myosins - genetics</topic><topic>Cardiology. Vascular system</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cohort Studies</topic><topic>Ebstein Anomaly - diagnostic imaging</topic><topic>Ebstein Anomaly - genetics</topic><topic>Family</topic><topic>Female</topic><topic>General aspects. Genetic counseling</topic><topic>Heart</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation - genetics</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myosin Heavy Chains - chemistry</topic><topic>Myosin Heavy Chains - genetics</topic><topic>Pedigree</topic><topic>Sarcomeres - genetics</topic><topic>Ultrasonography</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Postma, Alex V</creatorcontrib><creatorcontrib>van Engelen, Klaartje</creatorcontrib><creatorcontrib>van de Meerakker, Judith</creatorcontrib><creatorcontrib>Rahman, Thahira</creatorcontrib><creatorcontrib>Probst, Susanne</creatorcontrib><creatorcontrib>Baars, Marieke J.H</creatorcontrib><creatorcontrib>Bauer, Ulrike</creatorcontrib><creatorcontrib>Pickardt, Thomas</creatorcontrib><creatorcontrib>Sperling, Silke R</creatorcontrib><creatorcontrib>Berger, Felix</creatorcontrib><creatorcontrib>Moorman, Antoon F.M</creatorcontrib><creatorcontrib>Mulder, Barbara J.M</creatorcontrib><creatorcontrib>Thierfelder, Ludwig</creatorcontrib><creatorcontrib>Keavney, Bernard</creatorcontrib><creatorcontrib>Goodship, Judith</creatorcontrib><creatorcontrib>Klaassen, Sabine</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation. Cardiovascular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Postma, Alex V</au><au>van Engelen, Klaartje</au><au>van de Meerakker, Judith</au><au>Rahman, Thahira</au><au>Probst, Susanne</au><au>Baars, Marieke J.H</au><au>Bauer, Ulrike</au><au>Pickardt, Thomas</au><au>Sperling, Silke R</au><au>Berger, Felix</au><au>Moorman, Antoon F.M</au><au>Mulder, Barbara J.M</au><au>Thierfelder, Ludwig</au><au>Keavney, Bernard</au><au>Goodship, Judith</au><au>Klaassen, Sabine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly</atitle><jtitle>Circulation. Cardiovascular genetics</jtitle><addtitle>Circ Cardiovasc Genet</addtitle><date>2011-02</date><risdate>2011</risdate><volume>4</volume><issue>1</issue><spage>43</spage><epage>50</epage><pages>43-50</pages><issn>1942-325X</issn><issn>1942-3268</issn><eissn>1942-3268</eissn><abstract>BACKGROUND—Ebstein anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding β-myosin heavy chain has been shown; in this report, we have screened for MYH7 mutations in a cohort of probands with Ebstein anomaly in a large population-based study.
METHODS AND RESULTS—Mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly was performed by next-generation sequencing and direct DNA sequencing of MYH7. Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found; 5 were novel and 2 were known to cause hypertrophic cardiomyopathy. All mutations except for 1 3-bp deletion were missense mutations; 1 was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein anomaly (P<0.0001). LVNC segregated with the MYH7 mutation in the pedigrees of 3 of the probands, 1 of which also included another individual with Ebstein anomaly.
CONCLUSIONS—Ebstein anomaly is a congenital heart malformation that is associated with mutations in MYH7. MYH7 mutations are predominantly found in Ebstein anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>21127202</pmid><doi>10.1161/CIRCGENETICS.110.957985</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Aged Amino Acid Sequence Biological and medical sciences Cardiac Myosins - chemistry Cardiac Myosins - genetics Cardiology. Vascular system Child Child, Preschool Cohort Studies Ebstein Anomaly - diagnostic imaging Ebstein Anomaly - genetics Family Female General aspects. Genetic counseling Heart Humans Infant Male Medical genetics Medical sciences Middle Aged Molecular Sequence Data Mutation - genetics Myocarditis. Cardiomyopathies Myosin Heavy Chains - chemistry Myosin Heavy Chains - genetics Pedigree Sarcomeres - genetics Ultrasonography Young Adult |
title | Mutations in the Sarcomere Gene MYH7 in Ebstein Anomaly |
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