This report describes congenital myopathy 6 with ophthalmoplegia (CMYP6), also called myopathy, proximal, and ophthalmoplegia or inclusion body myopathy 3. There are both dominant and recessive forms of CMYP6. The human gene implicated in this disease is MYH2, which encodes the myosin heavy chain isoform that is expressed in fast type 2A muscle fibers in skeletal muscle. In flies there is one gene, Mhc, orthologous to ten genes in humans that encode forms of muscle myosin class II heavy chain, including MYH2. Classical amorphic and hypomorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Mhc gene.
The human MYH2 gene has not been introduced into flies.
Phenotypes of amorphic alleles of Mhc range from lethality to flight defective; defects in myofibrils and sacromeres are observed.
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): E701K in the fly Mhc gene (corresponds to E706K in the human MYH2 gene). The disease model in flies makes use of a transgene carrying this mutation in Mhc in a genetic background homozygous for a flightless Mhc allele. See the 'Disease-Implicate Variants' table below.
[updated Jul. 2023 by FlyBase; FBrf0222196]
Congenital myopathy is a term for any genetic muscle disorder that is typically noticed at birth and includes weakness and lack of muscle tone. Some congenital myopathies may not show symptoms until infancy or childhood. There are many types of congenital myopathy with varying severity. Some symptoms may remain stable or progress slowly. The following is a range of symptoms: lack of muscle control and weakness; difficulty breathing; difficulty eating; slow to reach developmental goals; delayed motor skills; skeletal problems. (https://www.ninds.nih.gov/health-information/disorders/congenital-myopathy#:~:text=Congenital%20myopathy)
[CONGENITAL MYOPATHY 6 WITH OPHTHALMOPLEGIA; CMYO6](https://omim.org/entry/605637)
[MYOSIN, HEAVY CHAIN 2, SKELETAL MUSCLE, ADULT; MYH2](https://omim.org/entry/160740)
Congenital myopathy 6 with ophthalmoplegia (CYMP6) is a relatively mild muscle disorder characterized by childhood onset of symptoms. The disorder is either slowly progressive or nonprogressive, and affected individuals retain ambulation, although there is variable severity. CYMP6 can show both autosomal dominant and autosomal recessive inheritance; the phenotype is similar in both forms (summary by Lossos et al., 2005; pubmed:15548556 and Tajsharghi et al., 2014; pubmed:24193343). [from MIM:605637; 2016.10.31]
Congenital myopathy 6 with ophthalmoplegia (CYMP6) is caused by heterozygous, compound heterozygous, or homozygous mutation in the gene encoding myosin heavy chain IIa (MYH2). [from MIM:605637; 2016.10.31]
The MYH2 gene encodes the myosin heavy chain isoform that is expressed in fast type 2A muscle fibers (summary by Tajsharghi et al., 2014; pubmed:24193343). [from MIM:160740; 2016.10.31]
Many to one: 10 human to 1 Drosophila.
Ortholog of human muscle myosin heavy chain genes, class II (1 Drosophila to 10 human); Dmel\Mhc shares 58% identity and 75% similarity with human MYH2.
