The combination of left ventricular non-compaction and hypertrophic cardiomyopathy in one family with a pathogenic variant in the MYBPC3 gene (rs397516037)

The article presents the results of clinical, instrumental and molecular genetic tests of three generations of a family with inherited cardiomyopathy caused by a new variant in the MYBPC3 gene. A specific feature of this case is the phenotypic heterogeneity of the mutation — a combination of hypertrophic cardiomyopathy and left ventricular non-compaction in family members. Attention is drawn to the various severity of clinical manifestations in relatives of carriers of mutation: from asymptomatic to severe heart failure and acute cerebrovascular accident.

1. Myasnikov RP, Shcherbakova NV, Kulikova ОV, et al. Des gene mutation in a family of proband with myofibrillary myopathy and non-compaction cardiomyopathy, resulted in cardiac transplantation. Russian Journal of Cardiology. 2017;(10):9-16. (In Russ.). doi:10.15829/1560-4071-2017-10-9-16.

2. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left Ventricular Non-Compaction. Journal of the American College of Cardiology. 2005;46(1):101-5. doi:10.1016/j.jacc.2005.03.045.

3. Jacquier A, Thuny F, Jop B, et al. Measurement of trabeculated left ventricular mass using cardiac magnetic resonance imaging in the diagnosis of left ventricular noncompaction. European Heart Journal. 2010;31(9):1098-104. doi:10.1093/eurheartj/ehp595.

4. Luther PK, Winkler H, Taylor K, et al. Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(28):11423-8. doi:10.1073/pnas.1103216108.

5. Previs MJ, Beck Previs S, Gulick J, et al. Molecular mechanics of cardiac myosinbinding protein C in native thick filaments. Science. 2012;337(6099):1215-8. doi:10.1126/ science.1223602.

6. Watkins H, Conner D, Thierfelder L, et al. Mutations in the cardiac myosin binding protein– C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nature Genetics. 1995;11(4):434-7. doi:10.1038/ng1295-434.

7. Daehmlow S, Erdmann J, Knueppel T, et al. Novel mutations in sarcomeric protein genes in dilated cardiomyopathy. Biochemical and Biophysical Research Communications. 2002;298(1):116-20. doi:10.1016/S0006-291X(02)02374-4.

8. Probst S, Oechslin E, Schuler P, et al. Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circulation Cardiovascular genetics. 2011;4(4):367-74. doi:10.1161/CIRCGENETICS.110.959270.

9. Sedaghat-Hamedani F, Haas J, Zhu F, et al. Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy. European Heart Journal. 2017;38(46):3449-60. doi:10.1093/eurheartj/ehx545.

10. Richard P, Ader F, Roux M, et al. Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity. Clinical Genetics. 2019;95(3):356-67. doi:10.1111/cge.13484.

11. van Waning JI, Moesker J, Heijsman D, et al. Systematic Review of Genotype-Phenotype Correlations in Noncompaction Cardiomyopathy. Journal of the American Heart Association. 2019;8(23):e012993. doi:10.1161/JAHA.119.012993.

12. van Waning JI, Caliskan K, Michels M, et al. Cardiac Phenotypes, Genetics, and Risks in Familial Noncompaction Cardiomyopathy. Journal of the American College of Cardiology. 2019;73(13):1601-11. doi:10.1016/j.jacc.2018.12.085.