title: Limb-Girdle Muscular Dystrophy Type 2A Resulting From c.C479G and c.G1818A Mutations in the Calpain-3 Gene.
abstract: Limb-Girdle Muscular Dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized by progressive weakness of proximal muscles. Here, we describe a patient with clinical features consistent with LGMD2A who harbors 2 rare changes in the CAPN3 gene sequence of unknown clinical significance. Mechanisms by which these 2 mutations could affect the protein are discussed. The c.C479G mutation seems to affect the proteolytic domain of calpain-3. Whereas the novel mutation c.G1818A seems to affect mRNA translation of the protein region involved in titin binding. We strongly believe that these genomic variants in CAPN3 are indeed deleterious and thus are currently misclassified. Since LGMD2 is considered a disorder of autosomal recessive inheritance, further population studies involving the molecular characterization of symptomatic patients must be performed as well as in vitro studies to ascertain the functional effects of these specific variants.
authors.affiliation: Departments of *Physical Medicine, Rehabilitation and Sport Medicine, and †Biochemistry and Pediatrics, University of Puerto Rico School of Medicine, San Juan, PR.
authors.forename: Edwardo
authors.initials: E
authors.lastname: Ramos
authors.forename: Sherly
authors.initials: S
authors.lastname: Pardo
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Mas Rodríguez
authors.forename: John
authors.initials: J
authors.lastname: Vélez
mesh_terms: D002154:Calpain / Q000235:genetics*; D002648:Child; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain