Mutations in the sarcomere gene MYH7 in Ebstein anomaly

Alex V. Postma, Klaartje Van Engelen, Judith Van De Meerakker, Thahira Rahman, Susanne Probst, Marieke J.H. Baars, Ulrike Bauer, Thomas Pickardt, Silke R. Sperling, Felix Berger, Antoon F.M. Moorman, Barbara J.M. Mulder, Ludwig Thierfelder, Bernard Keavney, Judith Goodship, Sabine Klaassen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalCirculation: Cardiovascular Genetics
Issue number1
Publication statusPublished - Feb 2011

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