Key result
ACTN2 missense variants were identified as the genetic cause of a novel autosomal dominant distal myopathy, termed actininopathy, in 4 affected families.
Why the study?
To clinically and pathologically characterize a cohort of patients presenting with a novel form of distal myopathy and identify the genetic cause of this new muscular dystrophy.
Observational
Yes
Identifies ACTN2 missense mutations as the genetic cause of a novel autosomal dominant distal myopathy termed actininopathy.
Does not yet warrant ACTN2 screening in distal myopathies; leaves open replication of actininopathy in larger cohorts.
OBJECTIVE: To clinically and pathologically characterize a cohort of patients presenting with a novel form of distal myopathy and to identify the genetic cause of this new muscular dystrophy. METHODS: We studied 4 families (3 from Spain and 1 from Sweden) suffering from an autosomal dominant distal myopathy. Affected members showed adult onset asymmetric distal muscle weakness with initial involvement of ankle dorsiflexion later progressing also to proximal limb muscles. RESULTS: In all 3 Spanish families, we identified a unique missense variant in the ACTN2 gene cosegregating with the disease. The affected members of the Swedish family carry a different ACTN2 missense variant. INTERPRETATION: ACTN2 encodes for alpha actinin2, which is highly expressed in the sarcomeric Z-disk with a major structural and functional role. Actininopathy is thus a new genetically determined distal myopathy. ANN NEUROL 2019;85:899-906.
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Savarese et al. (2019) conducted an observational in Autosomal dominant distal myopathy. ACTN2 missense variants was evaluated on Genetic cause of the new muscular dystrophy. ACTN2 missense variants were identified as the genetic cause of a novel autosomal dominant distal myopathy, termed actininopathy, in 4 affected families.
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