Clinical and Genetic Characterization of CAPN3-Related Limb-Girdle Muscular Dystrophies in an Egyptian Cohort

Limb-girdle muscular dystrophies (LGMDs) are a group of genetic disorders marked by progressive weakness and atrophy of proximal limb muscles. Calpainopathy is the most prevalent autosomal recessive form (LGMD-R1), caused by biallelic variants in the CAPN3 gene, whereas the less common autosomal dominant (LGMD-D4) results from a heterozygous variation.

This retrospective study elaborates on the clinical and molecular characteristics of patients with CAPN3-related dystrophies in an Egyptian cohort of 48 LGMD patients.

Exome sequencing identified 13 CAPN3 variants in 12 LGMD-R1 patients and one with LGMD-D4. Among these, two novel missense variants were described: c.581C>T (p.Ser194Phe) and c.1536G>C (p.Glu512Asp). More than half of the revealed variants were missense mutations, a finding that is consistent with previous studies in other populations. A genotype-phenotype correlation could not be established, particularly due to the presence of inter- and intrafamilial variability. This study supports the increased prevalence of (c.1343G>A, p.Arg448His) and (c.1027G>T, p.Glu343∗) variants in Egyptian patients.

Given the high rate of consanguinity in Egypt, further extensive studies focusing on the genetic modifiers in the disease progression and the role of environmental factors are recommended.