A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family

Neuromuscul Disord. 2015 Feb;25(2):155-60. doi: 10.1016/j.nmd.2014.09.007. Epub 2014 Sep 28.

Abstract

Authors describe clinical, pathological, imaging and genetic findings in the first Irish family with Laing distal myopathy in whom a novel mutation in the human slow β-myosin heavy chain (MYH7) gene has been identified. A kindred of 14 over 6 generations included 6 individuals with childhood onset distal lower limb weakness in a scapula-peroneal distribution with subsequent proximal upper and lower limb weakness. Finger extensor weakness especially in the 3rd-5th fingers was present in each and two patients had "hanging big toe" sign. Three patients were non-ambulatory by middle-age. One patient developed cardiomyopathy and two patients had respiratory muscle impairment. Intriguingly, brain white matter lesions and epilepsy were present in three patients. Muscle biopsy revealed fibre-size variation, rimmed vacuoles, mild-extensive central nucleation, redundant and folded sarcolemmal membrane and Z band streaming. Genetic analysis revealed a novel heterozygous mutation in the MYH7 gene in one patient which co-segregated perfectly in the remaining 5 affected members and was absent in six unaffected members.

Keywords: Brain white matter disease; Epilepsy; Laing distal myopathy; MYH7.

MeSH terms

  • Adult
  • Aged
  • Brain / pathology
  • Cardiac Myosins / genetics*
  • Creatine Kinase / blood
  • Distal Myopathies / blood
  • Distal Myopathies / complications
  • Distal Myopathies / genetics*
  • Electromyography
  • Epilepsy / etiology
  • Family Health
  • Female
  • Humans
  • Ireland
  • Leucine / genetics*
  • Male
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Mutation / genetics*
  • Myosin Heavy Chains / genetics*
  • Proline / genetics*

Substances

  • MYH7 protein, human
  • Proline
  • Creatine Kinase
  • Cardiac Myosins
  • Myosin Heavy Chains
  • Leucine