title: Mutations of CAPN3 in Korean patients with limb-girdle muscular dystrophy.
abstract: The limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessively inherited disease caused by a mutation of the calpain 3 gene (CAPN3), and is considered one of the most prevalent subtypes of limb-girdle muscular dystrophy (LGMD). In this study, we aimed to identify CAPN3 mutations and to characterize the phenotype of Korean patients with LGMD2A. Among 35 patients with LGMD, four patients, who showed calpain 3 deficiency on western blot analysis, were analyzed in this study. Total RNA extracted from frozen muscle tissue was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) using six primer pairs covering all coding sequences of CAPN3, and direct sequencing was performed. Clinical and pathological features of the patients were also reviewed. We found four different mutations in five alleles from three patients. Of the pathogenic mutations identified, two were novel (c.2125T>C and c.2355-2357delTTC), and the others had been reported elsewhere (c.440G>C, c.1076C>T). All patients showed a high CK level with predominant proximal leg weakness, and the onset was in their childhood except for one patient. Among two novel CAPN3 mutations, one was a missense mutation (c.2125T>C [p.709Ser>Pro]), and the other was a small in-frame deletion causing omission of a single amino acid (c.2355-2357delTTC [p.786delPhe]). The clinical features of our patients were generally compatible with the characteristics of LGMD2A patients described in the previous studies.
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, University Hospital, 1-ga 10, Ami-dong, Seo-gu, Busan, Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.forename: Hyang-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Cheol-Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Kyu-Hyun
authors.initials: KH
authors.lastname: Park
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002154:Calpain / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain