A rare homozygous <i>CAPN3</i> variant with distinct clinical features in unrelated families of Iraqi Jewish descent

<i>CAPN3</i> encodes a calcium-activated skeletal muscle-specific protease. Pathogenic variants in <i>CAPN3</i> are associated with autosomal recessive and dominant limb-girdle muscular dystrophy. We report on three children and one adult from four unrelated Iraqi Jewish families, who harbor the same homozygous variant in <i>CAPN3</i>, p.Gln123Lys. Patients shared recognizable features of toe-walking and elevated creatine phosphokinase since childhood. The variant affects a conserved protein domain common to the calpain super family and likely represents a founder mutation in individuals of Iraqi Jewish ancestry. Our findings have potential implications on screening in relevant populations, allowing for more prompt diagnoses and future therapies.