Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation

Neuromuscul Disord. 2006 Oct;16(9-10):548-52. doi: 10.1016/j.nmd.2006.07.005. Epub 2006 Sep 1.

Abstract

We report on a 2-year-old male child with both nemaline myopathy and hypertrophic cardiomyopathy (HCM). Sequencing of the ACTA1 gene showed a "de novo" missense heterozygous mutation a>g in exon 7 (Lys336Glu). Two-dimensional electrophoresis showed 28% mutant actin present in his muscle biopsy. Actin was isolated from the muscle biopsy and examined by in vitro motility assay. The sliding speed was 13+/-3% less than normal and the affinity of actin for the Z-line protein alpha-actinin was reduced 10 fold. This is the first report on a hypertrophic cardiomyopathy associated with nemaline myopathy and an ACTA1 mutation.

Publication types

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

MeSH terms

  • Actinin / metabolism
  • Actins / genetics*
  • Amino Acid Substitution / genetics
  • Cardiomyopathy, Hypertrophic, Familial / complications
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / physiopathology
  • Child, Preschool
  • DNA Mutational Analysis
  • Fatal Outcome
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Glutamic Acid / genetics
  • Humans
  • Lysine / genetics
  • Male
  • Muscle Contraction / genetics
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Mutation, Missense / genetics*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myopathies, Nemaline / complications
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / physiopathology

Substances

  • Actins
  • Actinin
  • Glutamic Acid
  • Lysine