De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy

Neuromuscul Disord. 2002 Dec;12(10):947-51. doi: 10.1016/s0960-8966(02)00182-7.

Abstract

We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis. In this patient, we demonstrate heterozygosity for a de novo CGT-CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation identified in a constitutively expressed exon of TPM3 in a nemaline myopathy patient, but is similar to recently described mutations in beta-tropomyosin (TPM2) associated with nemaline myopathy and mutations in fast alpha-tropomyosin (TPM1) which cause hypertrophic cardiomyopathy.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adolescent
  • Arginine / genetics
  • DNA Mutational Analysis
  • Drosophila Proteins*
  • Exons
  • Female
  • Genetic Carrier Screening
  • Histidine / genetics
  • Humans
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / pathology
  • Muscle Fibers, Skeletal / ultrastructure
  • Muscle Weakness / etiology
  • Muscle Weakness / genetics
  • Mutation, Missense
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / physiopathology
  • Myopathies, Nemaline / ultrastructure
  • Tropomyosin / genetics*

Substances

  • Drosophila Proteins
  • TPM1 protein, human
  • TPM3 protein, human
  • Tm2 protein, Drosophila
  • Tpm1 protein, mouse
  • Tropomyosin
  • Histidine
  • Arginine
  • Adenosine Triphosphatases