G.P.230: Clinical and genetic features in Korean patients with CAPN3 mutations

Abstract

Recessive mutations in the CAPN3 gene are responsible for Limb-girdle muscular dystrophy (LGMD) 2A, one of the most common type of LGMD worldwide. However, the characteristics of LGMD2A in Koreans have not yet been evaluated. Therefore, the present study was designed to investigate the characteristics in Korean patients with CAPN3 mutations. Mutations were identified by direct or targeted sequencing using a primer set that covered all 24 exons and flanking intron regions of the CAPN3 gene. Then, we evaluated genetic, clinical, and pathological spectrum. Results: We identified eight distinct mutations in 12 patients from nine families. Four mutations were missense, two were frameshift, and two were aberrant splicing. Additionally, four mutations (c.1524+1G>T, c.1789_1790inA, c.2120A>G, c.2384C>T) were novel. We detected two mutations in eight patients from six families and only one mutation in four patients from three families. Patient ages at symptom onset ranged from eight to 33 years. Family history was positive in four of nine families. Three patients were initially diagnosed with Emery-Dreifuss muscular dystrophy, hyperCKemia, and polymyositis, respectively. This is because one patient exhibited prominent contracture of ankle and elbow joints, another patient presented hyperCKemia without definite muscle weakness, and the other patient showed minimal inflammatory cell infiltration on muscle pathology. Winged scapula, joint contracture and lordosis were found in four, six and three patients, respectively. In addition, lobulated fibers on muscle pathology were detected in four of eight tested patients. In the present study, we identify four novel CAPN3 mutations and confirm the usefulness of clinical and pathologic findings, especially lobulated fibers.