This report describes congenital myopathy 2A, typical, autosomal dominant (CMYO2A), which is a subtype of nemaline myopathy; both autosomal dominant and autosomal recessive forms of CMYO2A have been described. The gene implicated in this disease is ACTA1, which encodes the alpha actin found in human skeletal muscle. CMYO2A is one of several myopathies associated with defects in the human ACTA1 gene; see the human disease model report 'myopathy, congenital, ACTA1-related' (FBhh0000581).
The human ACTA1 gene has not been introduced into flies.
Many variants associated with CMYO2A have been investigated in flies, as analogous mutations in the fly Act88F gene. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G16R in the fly Act88F gene [corresponds to G17R (G15R) in the human ACTA1 gene]; V164M in the fly Act88F gene [corresponds to V165M (V163M) in the human ACTA1 gene]; V164L in the fly Act88F gene [corresponds to V165L (V163L) in the human ACTA1 gene]; I137M in the fly Act88F gene [corresponds to I138M (I136M) in the human ACTA1 gene]; D155N in the fly Act88F gene [corresponds to D156N (D154N) in the human ACTA1 gene]; G269D in the fly Act88F gene [corresponds to G270D (G268D) in the human ACTA1 gene]; R257C in the fly Act88F gene [corresponds to R258C (R256C) in the human ACTA1 gene]; R373H in the fly Act88F gene [corresponds to R374H (R372H) in the human ACTA1 gene]; A139V in the fly Act88F gene [corresponds to A140V (A138V) in the human ACTA1 gene, designated Act88FM320.
[updated July 2023 by FlyBase; FBrf0222196]
Nemaline myopathy is a form of congenital myopathy; the clinical phenotype is highly variable, with differing age at onset and of severity. Muscle weakness typically involves proximal muscles, with involvement of the facial, bulbar, and respiratory muscles (Ilkovski et al., 2001; pubmed:11333380). Typical nemaline myopathy is the most common form, presenting as infantile hypotonia and muscle weakness. It is slowly progressive or nonprogressive, and most adults achieve ambulation. The severe form of the disorder is characterized by absence of spontaneous movement or respiration at birth, arthrogryposis, and death in the first months of life. Much less commonly, late-childhood or adult-onset can occur (Wallgren-Pettersson et al., 1999, pubmed:10619714; Sanoudou and Beggs, 2001, pubmed:11516997). [from MIM:161800; 2017.07.24]
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 2A, TYPICAL, AUTOSOMAL DOMINANT; CMYO2A](https://omim.org/entry/161800)
[ACTIN, ALPHA-1, SKELETAL MUSCLE; ACTA1](https://omim.org/entry/102610)
See general description of nemaline myopathy, above.
Congenital myopathy-23 (CMYO23) is caused by heterozygous mutation in the tropomyosin-2 gene on chromosome 9p13. [from MIM:609285; 2026.07.22]
Heterozygous mutation in the TPM2 gene can also cause distal arthrogryposis type 1A (DA1A; MIM:108120, FBhh0001427), which shows similar features and may represent the same disease. [from MIM:108120; 2022.01.16]
Nemaline myopathy shows both autosomal dominant and autosomal recessive inheritance. Nemaline myopathy 3 (NEM3) is caused by homozygous, compound heterozygous, or heterozygous mutation in the alpha-actin-1 gene (ACTA1). [from MIM:161800; 2017.07.24]
Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. [from Gene Cards, ACTA1; 2017.07.24]
The ACTA1 gene encodes skeletal muscle alpha-actin, the principal actin isoform in adult skeletal muscle, which forms the core of the thin filament of the sarcomere where it interacts with a variety of proteins to produce the force for muscle contraction (Laing et al., 2009; pubmed:19562689). [from MIM:102610; 2017.07.24]
Many to many: there are multiple actins in both species.
There are multiple actins in both species (many to many). The actins are very highly conserved; Dmel\Act88F shares 93% identity and 96% similarity with the human ACTA1 gene; it shares a similar level of orthology with human ACTA2 and a slightly higher level with ACTB (96% identity and 99% similarity).
