Details of Disease

General Information of Disease (ID: DISE0PV2)

• Disease Name: Alpha-actinopathy
• Synonyms: actin myopathy; actinopathy; ACTA1 disease; alpha actinopathy; alpha-actinopathy
• Definition: A musculoskeletal system disorder that covers a wide spectrum of phenotypes and is caused by pathogenic variants in the skeletal muscle -actin gene (ACTA1). These variants lead to a variety of overlapping adult onset and congenital myopathies characterized by muscle weakness, hypotonia, myopathic face, respiratory dysfunction, and rarely cardiac involvement. Specific skeletal muscle structural lesions visible on muscle biopsy include actin accumulations, nemaline and intranuclear bodies, fiber-type disproportion, cores, caps, dystrophic features and zebra bodies. Disorders associated with ACTA1 pathogenic variants can have autosomal dominant (90%) or recessive (10%) inheritance.|The most penetrant phenotype among all of the actinopathy disease entities is muscular weakness. While nemaline myopathy is the most common presentation, several other myopathies have been reported in association with ACTA1 mutations. The absence of clearly defined and/or distinct differences in molecular mechanism, coupled with noted phenotypic variability (both intra- and inter-familial) for individual variants, indicates that these entities are part of the same clinical spectrum.
• Disease Hierarchy:
  DIS2BIP8: Congenital nervous system disorder
  DISLSK9G: Congenital myopathy
  DISD715V: Hereditary neurological disease
  DISXXXEE: Qualitative or quantitative protein defects in neuromuscular diseases
  DISE0PV2: Alpha-actinopathy

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACTA1	OTOVGLPG	Definitive	Autosomal recessive	[1]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.