ACTA1-myopathy with prominent finger flexor weakness and rimmed vacuoles

Neuromuscul Disord. 2019 May;29(5):388-391. doi: 10.1016/j.nmd.2019.02.012. Epub 2019 Mar 2.

Abstract

Actinopathy is a group of clinically and pathologically heterogeneous myopathies due to mutations in the skeletal muscle sarcomeric α-actin 1-encoding gene (ACTA1). Disease-onset spans from prenatal life to adulthood and weakness can preferentially affect proximal or distal muscles. Myopathological findings include a spectrum of structural abnormalities with nemaline rods being the most common. We report a daughter and father with prominent finger flexors and/or quadriceps involvement. Muscle biopsies revealed rimmed vacuoles in both patients, associated with type 1 fiber atrophy in the daughter, and nemaline rods in the father. Next generation sequencing identified a novel dominant ACTA1 variant, c.149G>A (p.Gly50Asp) in both individuals and no abnormal variants in vacuolar myopathy-associated genes. Our findings expand the clinico-pathological spectrum of actinopathy.

Keywords: ACTA1; Congenital fiber type disproportion; Finger flexor weakness; IBM; Inclusion body myositis; Nemaline myopathy; Rimmed vacuoles.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Adult
  • Aged
  • Fathers
  • Female
  • Fingers
  • Humans
  • Male
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / physiopathology*
  • Nuclear Family
  • Quadriceps Muscle / pathology
  • Quadriceps Muscle / physiopathology*
  • Vacuoles / pathology

Substances

  • ACTA1 protein, human
  • Actins

Supplementary concepts

  • Actin-Accumulation Myopathy