2. Academic Validation
  3. Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations

Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations

  • Ann Neurol. 2019 Jun;85(6):899-906. doi: 10.1002/ana.25470.
Marco Savarese 1 2,  Johanna Palmio 3,  Juan José Poza 4,  Jan Weinberg 5,  Montse Olive 6,  Ana Maria Cobo 7,  Anna Vihola 1 2,  Per Harald Jonson 1 2,  Jaakko Sarparanta 1 2,  Federico García-Bragado 4,  Jon Andoni Urtizberea 7,  Peter Hackman 1 2,  Bjarne Udd 1 2 3 8
Affiliations

Affiliations

  • 1 Folkhälsan Research Center, Helsinki, Finland.
  • 2 Medicum, University of Helsinki, Helsinki, Finland.
  • 3 Neuromuscular Research Center, Tampere University Hospital and Tampere University, Tampere, Finland.
  • 4 Department of Neurology, Donostia University Hospital, San Sebastián, Spain.
  • 5 Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
  • 6 Department of Pathology, Neuropathology and Neuromuscular Unit, Biomedical Research Institute of Bellvitge, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.
  • 7 Neuromuscular Diseases Center of Competence, Marin Hospital, Public Hospital Network of Paris, Hendaye, France.
  • 8 Department of Neurology, Vaasa Central Hospital, Vaasa, Finland.
PMID: 30900782 DOI: 10.1002/ana.25470
Abstract

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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