This report describes cardiomyopathy, familial hypertrophic 10 (CMH10), a subtype of familial hypertrophic cardiomyopathy. CMH10 typically exhibits autosomal dominant inheritance, but a severe recessive form has recently been characterized. The gene implicated in this disease is MYL2, which encodes a myosin regulatory light chain. There are multiple myosin light chain genes in both human and flies. In Drosophila, the gene most closely related to human MYL2 is Mlc2, for which a classic loss-of-function allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of human Hsap\MYL2 have been introduced into flies, including wild-type and variants implicated in disease. Partial heterologous rescue (functional complementation) of Dmel\Mlc2 heart-specific phenotypes is observed using the wild-type human gene, but not for the variants characterized. Variant(s) implicated in human disease tested (as transgenic human gene, MYL2): the G162R and P144,fs variant forms of the human gene have been introduced into flies. This frameshift variant is associated with the severe recessive form of CMH10.
Animals homozygous for a loss-of-function allele of Dmel\Mlc2 typically die during the embryonic stage; heterozygotes exhibit a flightless phenotype due to sarcomeric structural abnormalities affecting the indirect flight muscles. Knockdown of Mlc2 specifically in the heart, effected by RNAi, results in abnormalities in larval heart contraction rhythm and reduced viability to adulthood. Genetic and physical interactions have been described for Dmel\Mlc2; see below and in the Mlc2 gene report.
[updated Jul. 2020 by FlyBase; FBrf0222196]
Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of cardiac muscle. Thickening usually occurs in the interventricular septum, the muscular wall that separates the left ventricle from the right ventricle. Cardiac hypertrophy often begins in adolescence or young adulthood, although it can develop at any time throughout life. The symptoms are variable, even within the same family. While most people this condition are symptom-free or have only mild symptoms, hypertrophic cardiomyopathy can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation. [from Genetics Home Reference, familial hypertrophic cardiomyopathy; 2016.10.13]
Hypertrophic cardiomyopathy in early stages produces a presystolic gallop due to an atrial heart sound, and EKG changes of ventricular hypertrophy. Progressive ventricular outflow obstruction may cause palpitation associated with arrhythmia, congestive heart failure, and sudden death. Hypertrophic cardiomyopathy accounts for a significant number (exceeding 25% in one study) of sudden deaths of young athletes. [from MIM:192600; 2016.10.28]
[CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 10; CMH10](https://omim.org/entry/608758)
[MYOSIN, LIGHT CHAIN 2, REGULATORY, CARDIAC, SLOW; MYL2](https://omim.org/entry/160781)
CMH10 typically exhibits autosomal dominant inheritance (MIM:608758), but a severe recessive form has recently been characterized (FBrf0245856).
Familial hypertrophic cardiomyopathy-10 (CMH10) is caused by mutation in the MYL2 gene. [from MIM:608758; 2020.07.19]
Myosins are a large family of motor proteins that share the common features of ATP hydrolysis, actin binding and potential for kinetic energy transduction. MYL2 encodes the regulatory light chain associated with cardiac myosin beta heavy chain. Ca+ triggers the phosphorylation of regulatory light chain that in turn triggers contraction. [Gene Cards, MYL2; 2020.07.19]
Myosin light chain-2 (MYL2) is an important protein in the regulation of myosin ATPase activity in smooth muscle. [from MIM:160781; 2020.07.19]
Many to many: multiple related genes in both species. Most closely related to Drosophila Mlc2.
Multiple related genes in both species; most closely related to human MYL2.
