Mutation spectrum and health status in skeletal muscle channelopathies in Japan

Abstract Skeletal muscle channelopathies, including non-dystrophic myotonia and periodic paralysis, are rare hereditary disorders caused by mutations of various ion channel genes. To define the frequency of associated mutations of skeletal muscle channelopathies in Japan, clinical and genetic data of two academic institutions, which provides genetic analysis service, were reviewed. Of 105 unrelated pedigrees genetically confirmed, 66 pedigrees were non-dystrophic myotonias [CLCN1 (n = 30) and SCN4A (n = 36)], 11 were hyperkalemic periodic paralysis (SCN4A), and 28 were hypokalemic periodic paralysis [CACNA1S (n = 16)] and SCN4A (n = 12)]. Of the 30 families with myotonia congenita, dominant form (Thomsen type) consisted 67 %, and unique mutations, A298T, P480T, T539A, and M560T, not found in Western countries, were commonly identified in CLCN1. Hypokalemic periodic paralysis caused by SCN4A mutations consisted 43 % in Japan, which was much higher than previous reports. Furthermore, the quality of life of the patients was assessed using the patient-reported outcome measures, SF-36 and INQoL, for 41 patients. This study indicated that the etiology of skeletal muscle channelopathies in Japan was not identical to previous reports from Western countries, and provided crucial information for genetics as well as future therapeutic interventions.