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Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations
Author(s) -
Savarese Marco,
Palmio Johanna,
Poza Juan José,
Weinberg Jan,
Olive Montse,
Cobo Ana Maria,
Vihola Anna,
Jonson Per Harald,
Sarparanta Jaakko,
GarcíaBragado Federico,
Urtizberea Jon Andoni,
Hackman Peter,
Udd Bjarne
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25470
Subject(s) - missense mutation , myopathy , muscular dystrophy , medicine , weakness , genetics , physical medicine and rehabilitation , mutation , anatomy , pathology , biology , gene
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.