Recurrent <i>CAPN3</i> p.Asp753Asn Variant Supports a Potential Dominant Calpainopathy with Variable Clinical Expressivity.

ABSTRACT: Limb-Girdle Muscular Dystrophies (LGMDs) are genetically heterogeneous disorders primarily affecting proximal limb muscles. The most common form, LGMDR1, results from biallelic CAPN3 mutations encoding calpain-3, a muscle-specific protease. Recently, growing evidence implicates heterozygous CAPN3 variants in autosomal dominant disease (LGMDD4), with pathogenic mechanisms still incompletely understood. In a retrospective multicenter Italian study of patients harboring monoallelic CAPN3 variants (ClinicalTrials.gov NCT05956132), the p.Asp753Asn substitution was the most frequent change, detected in eight unrelated individuals. These patients, aged 6-80 years, exhibited a spectrum of presentations ranging from asymptomatic hyperCKemia and exertional myalgia to mild proxim

SUBMITTER: D'Este G 

PROVIDER: S-EPMC12692566 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature