RESUMEN
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.
Asunto(s)
Cardiomiopatías , No Compactación Aislada del Miocardio Ventricular , Humanos , No Compactación Aislada del Miocardio Ventricular/genética , Mutación , Corazón , Mutación Missense , Cadenas Pesadas de Miosina/genética , Miosinas Cardíacas/genéticaRESUMEN
Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype-phenotype correlations are the way to improve the precision of our diagnostics. We present a familial case of LVNC with arrhythmic and thrombotic complications, myocardial fibrosis and heart failure, cosegregating with the splicing variant in the FHOD3 gene. This is the first description of FHOD3-dependent LVNC to our knowledge. We also revise the assumed mechanism of pathogenesis in the case of FHOD3 splicing alterations.
