Unraveling Novel Pathogenic CAPN3 Variants in Limb-Girdle Muscular Dystrophy R1

Limb-Girdle Muscular Dystrophy R1 (LGMDR1) is an autosomal recessive neuromuscular disorder caused by mutations in the calpain-3 (CAPN3) gene, which encodes a calcium-dependent intracellular protease. Various pathogenic mutations have been reported to date, typically leading to weakness of the pelvic and shoulder girdle muscles. However, the clinical and pathological features of LGMDR1 are often heterogeneous and overlap with those of other LGMD subtypes, making a definitive molecular diagnosis essential for understanding the disease pathogenesis. Immunoblot analysis of calpain-3 protein revealed either complete or partial loss of expression in patients with LGMD. Additionally, multiple CAPN3 variants were identified and evaluated using in silico pathogenicity prediction tools. Alongside previously known mutations, Sanger sequencing also revealed novel pathogenic variants in the CAPN3 gene. Identification of genetic variants in LGMDR1 patients helps explore the mechanisms of disease pathogenesis and may support more accurate diagnosis and prognostication.