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.
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.
Authors: Mary Ella Pierpont; Martina Brueckner; Wendy K Chung; Vidu Garg; Ronald V Lacro; Amy L McGuire; Seema Mital; James R Priest; William T Pu; Amy Roberts; Stephanie M Ware; Bruce D Gelb; Mark W Russell Journal: Circulation Date: 2018-11-20 Impact factor: 29.690
Authors: Keenan C Taylor; Massimo Buvoli; Elif Nihal Korkmaz; Ada Buvoli; Yuqing Zheng; Nathan T Heinze; Qiang Cui; Leslie A Leinwand; Ivan Rayment Journal: Proc Natl Acad Sci U S A Date: 2015-07-06 Impact factor: 11.205
Authors: Gasnat Shaboodien; Timothy F Spracklen; Stephen Kamuli; Polycarp Ndibangwi; Carla Van Niekerk; Ntobeko A B Ntusi Journal: Cardiovasc Diagn Ther Date: 2020-04
Authors: Najim Lahrouchi; Alex V Postma; Christian M Salazar; Daniel M De Laughter; Fleur Tjong; Lenka Piherová; Forrest Z Bowling; Dominic Zimmerman; Elisabeth M Lodder; Asaf Ta-Shma; Zeev Perles; Leander Beekman; Aho Ilgun; Quinn Gunst; Mariam Hababa; Doris Škorić-Milosavljević; Viktor Stránecký; Viktor Tomek; Peter de Knijff; Rick de Leeuw; Jamille Y Robinson; Sabrina C Burn; Hiba Mustafa; Matthew Ambrose; Timothy Moss; Jennifer Jacober; Dmitriy M Niyazov; Barry Wolf; Katherine H Kim; Sara Cherny; Andreas Rousounides; Aphrodite Aristidou-Kallika; George Tanteles; Bruel Ange-Line; Anne-Sophie Denommé-Pichon; Christine Francannet; Damara Ortiz; Monique C Haak; Arend D.J. Ten Harkel; Gwendolyn Tr Manten; Annemiek C Dutman; Katelijne Bouman; Monia Magliozzi; Francesca Clementina Radio; Gijs We Santen; Johanna C Herkert; H Alex Brown; Orly Elpeleg; Maurice Jb van den Hoff; Barbara Mulder; Michael V Airola; Stanislav Kmoch; Joey V Barnett; Sally-Ann Clur; Michael A Frohman; Connie R Bezzina Journal: J Clin Invest Date: 2021-03-01 Impact factor: 14.808