• cardiomyopathy

This report describes fly models relevant to cardiomyopathies that are MYH7- or MYH6-related. The human genes implicated in these diseases encode cardiac muscle myosin class II heavy chains. Diseases associated with MYH7 (see MIM:160760) include cardiomyopathy, familial hypertrophic 1 (FBhh0000411) and dilated cardiomyopathy 1S (FBhh0000160); diseases associated with MYH6 (see MIM:160710) include cardiomyopathy, familial hypertrophic 14 (FBhh0000412) and dilated cardiomyopathy 1EE (FBhh0000159); most are inherited as autosomal dominants. Historically, MYH7 has been found to be one of the most common genes associated with hypertrophic cardiomyopathy (HCM)and involvement of MYH7 with hypertrophic cardiomyopathy is strongly supported by a large-scale WES analysis; association of MYH7 with dilated cardiomyopathy is more modestly supported (Walsh, et al., 2016; pubmed:27532257).

The human MYH7 gene has not been introduced into flies. The MYH6 gene has not been introduced into flies, with the exception of a GFP reporter construct using the Hsap\MYH6 promoter.

In flies there is one gene, Mhc, orthologous to the ten genes in humans that encode forms of muscle myosin class II heavy chain; MYH7 and MYH6 are reciprocal bests hits of Dmel\Mhc. Classical amorphic and hypomorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Mhc gene. Phenotypes of amorphic alleles of Mhc range from lethality to flight defective; defects in myofibrils and sarcomeres are observed. Extensive genetic and physical interactions of Dmel\Mhc have been described; see below and in the Mhc gene report.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): P837L in the fly Mhc gene (corresponds to P838L in the human MYH7 gene), implicated in cardiomyopathy, familial hypertrophic 1 (FBhh0000411) and has also been reported to result in familial restrictive cardiomyopathy (ClinVar:42910); R249Q in the fly Mhc gene (corresponds to R249Q in the human MYH7 gene) and R147N in the fly Mhc gene (corresponds to K146N in the human MYH7 gene), both implicated in cardiomyopathy, familial hypertrophic 1 (FBhh0000411); S531P in the fly Mhc gene (corresponds to S532P in the human MYH7 gene), implicated in dilated cardiomyopathy 1S (FBhh0000160). See the 'Disease-Implicated Variants' table, below.

[updated Oct. 2021 by FlyBase; FBrf0222196]