This report describes a fly model of congenital myopathy 7A, myosin storage, autosomal dominant (CMYP7A), also called myosin storage myopathy or autosomal dominant hyaline body myopathy. The human gene implicated in this disease (and also in the recessive form) is MYH7, which encodes a cardiac muscle myosin class II heavy chain. There are multiple forms of myopathy, cardiomyopathy, and related diseases associated with MYH7 (see MIM:160760). In flies there is one gene, Mhc, orthologous to the ten genes that encode forms of muscle myosin class II heavy chain in humans; MYH7 is a reciprocal best hit of Dmel\Mhc. Classical amorphic and hypomorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for the Mhc gene.
The human MYH7 gene has not been introduced into flies.
Work in flies has made use of transgenic constructs with variants introduced into the Mhc gene that are analogous to specific variants of MYH7 associated with CMYP7A. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): L1791P in the fly Mhc gene (corresponds to L1793P in the human MYH7 gene); R1843W in the fly Mhc gene (corresponds to R1845W in the human MYH7 gene). See the 'Disease-Implicated Variants' table below. A third variant implicated in the recessive form of this disease has also been characterized; see the human disease model report 'congenital myopathy 7B, myosin storage, autosomal recessive' (FBhh0000815).
No difference was found in the phenotypes of flies carrying the recessive variant (E1881K) vs. those carrying either of these two dominant variants (L1793P, R1845W). Flies expressing exclusively one of the mutant myosins exhibit severe impairment of flight and jump ability, progressively disrupted muscle ultrastructure, and myosin aggregates.
See also the human disease model report 'myopathy, MYH-class-II-related' (FBhh0000423).
[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 7A, MYOSIN STORAGE, AUTOSOMAL DOMINANT; CMYO7A](https://omim.org/entry/608358)
[MYOSIN, HEAVY CHAIN 7, CARDIAC MUSCLE, BETA; MYH7](https://omim.org/entry/160760)
Myosin storage myopathy is a condition that causes muscle weakness that does not progress or progresses very slowly over time. This condition is characterized by the formation of myosin protein aggregates within certain muscle fibers. Onset is usually during childhood, although it may be later. Because of muscle weakness, affected individuals may start walking later than usual and have a waddling gait, trouble climbing stairs, and difficulty lifting the arms above shoulder level. Muscle weakness also causes some affected individuals to have trouble breathing. [Genetics Home Reference, Myosin storage myopathy; 2018.05.24]
Autosomal dominant myosin storage congenital myopathy-7A (CMYP7A) is a skeletal muscle disorder with wide phenotypic variability. The age at symptom onset can range from early childhood to late adulthood. Affected individuals have proximal muscle weakness affecting the upper and lower limbs and distal muscle weakness of the lower limbs, resulting in gait difficulties and scapular winging (scapuloperoneal myopathy). Additional features may include thin habitus, high-arched palate, foot drop, pes cavus, calf pseudohypertrophy, and decreased reflexes. The severity is also variable: some patients develop respiratory insufficiency, joint contractures, and scoliosis in the first decades, whereas others are clinically unaffected, but show subtle signs of the disorder on examination. Serum creatine kinase may be normal or elevated. The disease is usually slowly progressive and most patients remain ambulatory. (Dye et al., 2006; pubmed:16684601; Pegoraro et al., 2007; pubmed:17336526; review by Tajsharghi and Oldfors, 2013; pubmed:22918376). [from MIM:608358; 2023.07.18]
Autosomal dominant myosin storage congenital myopathy-7A (CMYP7A) is caused by heterozygous mutation in the MYH7 gene on chromosome 14q11. Biallelic mutation in the MYH7 gene causes autosomal recessive myosin storage congenital myopathy-7B (FBhh0000815). [from MIM:608358; 2023.07.18]
Skeletal muscle biopsy can show different abnormalities, including hyaline bodies, type 1 fiber predominance, congenital fiber-type disproportion (CFTD), and nonspecific myopathic changes with myofibrillar disarray (summary by Dye et al., 2006; pubmed:16684601). [from MIM:608358; 2023.07.18]
The MYH7 gene encodes the beta-cardiac/slow skeletal myosin heavy chain (MyHC-slow), expressed predominantly in the cardiac ventricles and slow skeletal (type 1) myofibers. Myosin acts as a molecular motor through its interaction with actin of the thin filament, which is vital for skeletal muscle force generation (summary by Beecroft et al., 2019; pubmed:31130376). [from MIM:160760; 2023.07.18]
Many to one: 10 human to 1 Drosophila; MYH7 is a reciprocal best hit to Dmel\Mhc.
