title: Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations.
abstract: OBJECTIVE
  This study was designed to investigate the characteristics of Korean patients with calpainopathy.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  We identified four novel CAPN3 mutations and demonstrated clinical and pathological heterogeneity in Korean patients with calpainopathy.
authors.affiliation: Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.|Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department and Research Institute of Rehabilitation Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Rae
authors.initials: SR
authors.lastname: Cho
authors.affiliation: Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Kee Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Duhee
authors.initials: D
authors.lastname: Bang
authors.affiliation: Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea. jihyni@yuhs.ac.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea. ycchoi@yuhs.ac.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002154:Calpain / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D056910:Republic of Korea
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain
keywords: CAPN3; Limb girdle muscular dystrophy 2A; calpainopathy; genetic testing; lobulated fiber