Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations

• Published in: Yonsei medical journal 2016, 57(1), , pp.173-179
• Main Authors: Park, Hyung Jun, Jang, Hoon, Lee, Jung Hwan, Shin, Ha Young, Cho, Sung Rae, Park, Kee Duk, Bang, Duhee, Lee, Min Goo, Kim, Seung Min, Lee, Ji Hyun, Choi, Young Chul
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amino Acid Sequence; Asian Continental Ancestry Group - genetics; Calpain - genetics; Female; Genetic Testing; Humans; Male; Molecular Sequence Data; Muscle Proteins - genetics; Muscle, Skeletal - pathology; Muscular Dystrophies, Limb-Girdle - ethnology; Muscular Dystrophies, Limb-Girdle - genetics; Muscular Dystrophies, Limb-Girdle - pathology; Mutation; Original; Republic of Korea; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2016.57.1.173

This study was designed to investigate the characteristics of Korean patients with calpainopathy. Thirteen patients from ten unrelated families were diagnosed with calpainopathy via direct or targeted sequencing of the CAPN3 gene. Clinical, mutational, and pathological spectra were then analyzed. Nine different mutations, including four novel mutations (NM_000070: c.1524+1G>T, c.1789_1790inA, c.2184+1G>T, and c.2384C>T) were identified. The median age at symptom onset was 22 (interquartile range: 15-28). Common clinical findings were joint contracture in nine patients, winged scapula in four, and lordosis in one. However, we also found highly variable clinical features including early onset joint contractures, asymptomatic hyperCKemia, and heterogeneous clinical severity in three members of the same family. Four of nine muscle specimens revealed lobulated fibers, but three showed normal skeletal muscle histology. We identified four novel CAPN3 mutations and demonstrated clinical and pathological heterogeneity in Korean patients with calpainopathy.