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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 554599.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Mutations in the Sarcomere Protein Gene MYH7 in Ebstein's Anomaly
Authors:Postma, A. V.; van Engelen, K.; van de Meerakker, J.; Rahman, T.; Probst, S.; Baars, M. J.; Bauer, U.; Pickardt, T.; Sperling, S. R.; Berger, F.; Moorman, A. F.; Mulder, B. J.; Thierfelder, L.; Keavney, B.; Goodship, J.; Klaassen, S.
Language:English
Date of Publication (YYYY-MM-DD):2011-02-01
Title of Journal:Circulation: Cardiovascular Genetics
Journal Abbrev.:Circ Cardiovasc Genet
Volume:4
Issue / Number:1
Start Page:43
End Page:50
Copyright:© 2010, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited
Review Status:not specified
Audience:Not Specified
Abstract / Description:BACKGROUND: -Ebstein's 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's anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding beta-myosin heavy chain has been reported; here we have screened for MYH7 mutations in a cohort of probands with Ebstein's anomaly in a large population-based study. METHODS AND RESULTS: -Mutational analysis in a cohort of 141 unrelated probands with Ebstein's 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 (HCM). All mutations except for one 3-bp deletion were missense mutations, one 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's anomaly (p<0.0001). LVNC segregated with the MYH7 mutation in the pedigrees of three of the probands, one of which also included another individual with Ebstein's anomaly. CONCLUSIONS: -Ebstein's anomaly is a congenital heart malformation that is associated with mutations in MYH7. MYH7 mutations are predominantly found in Ebstein's anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.
Free Keywords:cardiomyopathy;
congenital;
genetics;
heart defects
Comment of the Author/Creator:Corresponding author; email: klaassen@mdc-berlin.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Academic Medical Center, Amsterdam, The Netherlands;
2.Institute of Human Genetics, Newcastle University, Newcastle, UK;
3.Max-Delbrück-Center for Molecular Medicine, Berlin, Germany;
4.National Registry for Congenital Heart Defects, Berlin, Germany;
5.German Heart Institute Berlin and Charité, University Medicine Berlin, Berlin, Germany;
6.Max-Delbrück-Ctr for Mol Med, German Heart Inst Berlin/Charité, Univ Med Berlin, Germany.
Identifiers:ISSN:1942-3268 [ID No:1]
URL:http://circgenetics.ahajournals.org/content/early/... [ID No:2]
DOI:10.1161/CIRCGENETICS.110.957985 [ID No:3]
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