Severe limb-girdle muscular dystrophy 2A in two young siblings from Guinea-Bissau associated with a novel null homozygous mutation in CAPN3 gene

Neuromuscul Disord. 2018 Dec;28(12):1003-1005. doi: 10.1016/j.nmd.2018.09.009. Epub 2018 Oct 9.

Abstract

Limb-girdle muscular dystrophy 2A (LGMD2A) or calpainopathy is the most common type of LGMD worldwide, representing about 30-40% of all described cases. Nevertheless, its prevalence in sub-Saharan African countries is unknown. We report two young siblings from Guinea-Bissau with recessive calpainopathy due to novel null homozygous c.1702Gdup mutation in CAPN3 gene. Their phenotype was quite aggressive concerning limb-girdle atrophy and muscle weakness as well as respiratory involvement. The proband needed nocturnal non-invasive ventilation at the age of 32, and his 33-year-old affected sister succumbed to an acute respiratory arrest after an intercurrent infection. This is the first description of calpainopathy in the sub-Saharian African region. Although there is no consistent genotype-phenotype correlation in calpainopathy, the new null homozygous mutation found in the CAPN3 gene may be associated with the particularly severe phenotype observed in our patients.

Keywords: Calpainopathy; Guinea-Bissau; Limb-girdle muscular dystrophy type 2A; Null homozygous mutation; Severe phenotype.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Calpain / genetics*
  • Female
  • Guinea-Bissau
  • Humans
  • Loss of Function Mutation*
  • Male
  • Muscle Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / diagnosis*
  • Muscular Dystrophies, Limb-Girdle / genetics
  • Severity of Illness Index
  • Siblings

Substances

  • Muscle Proteins
  • CAPN3 protein, human
  • Calpain

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2A