Protein-extending ACTN2 frameshift variants cause variable myopathy phenotypes by protein aggregation.

ABSTRACT:

Objective

The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha-actinin-2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha-actinin-2 is to link actin and titin to the sarcomere Z-disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype-phenotype correlations in ACTN2-related d

SUBMITTER: Ranta-Aho J 

PROVIDER: S-EPMC11537131 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature