A Splice Variant of the MYH7 Gene Is Causative in a Family with Isolated Left Ventricular Noncompaction Cardiomyopathy

Genes (Basel). 2022 Sep 28;13(10):1750. doi: 10.3390/genes13101750.

Abstract

Variants of the MYH7 gene have been associated with a number of primary cardiac conditions, including left ventricular noncompaction cardiomyopathy (LVNC). Most cases of MYH7-related diseases are associated with such variant types as missense substitutions and in-frame indels. Thus, truncating variants in MYH7 (MYH7tv) and associated mechanism of haploinsufficiency are usually considered not pathogenic in these disorders. However, recent large-scale studies demonstrated evidence of the significance of MYH7tv for LVNC and gave rise to an assumption that haploinsufficiency may be the causal mechanism for LVNC. In this article, we present a family with isolated LVNC and a heterozygous splice variant of the MYH7 gene, analyze possible consequences of this variant and conclude that not all variants that are predicted truncating really act through haploinsufficiency. This study can highlight the importance of a precise assessment of MYH7 splicing variants and their participation in the development of LVNC.

Keywords: MYH7; genetic testing; left ventricular noncompaction; splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiac Myosins / genetics
  • Cardiomyopathies*
  • Heart
  • Humans
  • Isolated Noncompaction of the Ventricular Myocardium* / genetics
  • Mutation
  • Mutation, Missense
  • Myosin Heavy Chains / genetics

Substances

  • MYH7 protein, human
  • Myosin Heavy Chains
  • Cardiac Myosins

Grants and funding

The study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2022-310).