Phenotypic and genetic spectrum of patients with limb-girdle muscular dystrophy type 2A from Serbia

Acta Myol. 2019 Sep 1;38(3):163-171. eCollection 2019 Sep.

Abstract

Limb-girdle muscular dystrophy (LGMD) type 2A (calpainopathy) is an autosomal recessive disease caused by mutation in the CAPN3 gene. The aim of this study was to examine genetic and phenotypic features of Serbian patients with calpainopathy. The study comprised 19 patients with genetically confirmed calpainopathy diagnosed at the Neurology Clinic, Clinical Center of Serbia and the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia during a ten-year period. Eighteen patients in this cohort had c.550delA mutation, with nine of them being homozygous. In majority of the patients, disease started in childhood or early adulthood. The disease affected shoulder girdle - upper arm and pelvic girdle - thigh muscles with similar frequency, with muscles of lower extremities being more severely impaired. Facial and bulbar muscles were spared. All patients in this cohort, except two, remained ambulant. None of the patients had cardiomyopathy, while 21% showed mild conduction defects. Respiratory function was mildly impaired in 21% of patients. Standard muscle histopathology showed myopathic and dystrophic pattern. In conclusion, the majority of Serbian LGMD2A patients have the same mutation and similar phenotype.

Keywords: c.550delA mutation; calpainopathy; muscle histopathology; muscle magnetic resonance imaging.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alleles
  • Biopsy
  • Calpain / genetics*
  • Child
  • Female
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Muscle Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / diagnostic imaging
  • Muscular Dystrophies, Limb-Girdle / epidemiology
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / physiopathology
  • Mutation
  • Phenotype
  • Serbia / epidemiology

Substances

  • Muscle Proteins
  • CAPN3 protein, human
  • Calpain

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2A