Mutation spectrum and health status in skeletal muscle channelopathies in Japan
Mutation spectrum and health status in skeletal muscle channelopathies in Japan
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DOI：
10.1016/j.nmd.2020.06.001
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发表时间：
2020-07-01
影响因子：
2.8
通讯作者：
Takahashi, Masanori P.
中科院分区：
文献类型：
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作者：
Sasaki, Ryogen;Nakaza, Maki;Takahashi, Masanori P.
骨骼肌通道病，包括非营养不良性肌强直和周期性麻痹，是由各种离子通道基因突变引起的罕见遗传性疾病。为了确定日本骨骼肌通道病相关突变的频率，回顾了两个提供遗传分析服务的学术机构的临床和遗传数据。在105个遗传学证实的无关家系中，66个家系为非营养不良性肌强直[CLCN 1（n = 30）和SCN 4A（n = 36）]，11个家系为高钾型周期性麻痹（SCN 4A），28个家系为低钾型周期性麻痹[CACNA 1 S（n = 16）和SCN 4A（n = 12）]。在30个先天性肌强直家族中，显性形式（Bclsen型）占67%，并且在CLCN 1中通常鉴定出在西方国家未发现的独特突变，A298 T，P480 T，T539 A和M560 T。在日本，由SCN 4A突变引起的低钾型周期性麻痹占43%，远高于以往的报道。此外，使用患者报告的结局指标SF-36和INQoL评估了41例患者的生活质量。这项研究表明，日本骨骼肌通道病的病因与西方国家以前的报道不相同，并为遗传学和未来的治疗干预提供了重要信息。(C)2020爱思唯尔B. V.保留所有权利。
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. (C) 2020 Elsevier B.V. All rights reserved.