Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients

Neuromuscul Disord. 2012 Nov;22(11):934-43. doi: 10.1016/j.nmd.2012.05.001. Epub 2012 Jun 27.

Abstract

Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2% of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anoctamins
  • Chloride Channels / genetics*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Italy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle, Skeletal / physiopathology*
  • Muscular Atrophy / etiology
  • Muscular Dystrophies, Limb-Girdle / complications
  • Muscular Dystrophies, Limb-Girdle / diagnosis
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation / genetics*
  • Pedigree

Substances

  • ANO5 protein, human
  • Anoctamins
  • Chloride Channels