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

Highlights • Calpainopathy is the most common type of LGMD worldwide. • First description of calpainopathy in sub-Saharan African region. • A novel null homozygous c.1702dup mutation was found in the CAPN3 gene. • Our two young siblings exhibited a particularly severe phenotype. 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. [ABSTRACT FROM AUTHOR]