臨床神経学

<シンポジウム(2)―10―5>ここまで分かった筋疾患

先天性筋無力症候群

大野 欽司

名古屋大学医学系研究科神経遺伝情報学〔〒466―8550 名古屋市昭和区鶴舞町65〕

Congenital myasthenic syndromes (CMS) are caused by germline mutations of molecules expressed at the neuromuscular junction (NMJ). Mutations in 11 molecules encoded by 15 genes have been reported in association with CMS. CMS can be classified into four clinical categories. First, missense mutations in the acetylcholine receptor (AChR) subunits lead to slow- and fast-channel syndromes. Second, mutations in the AChR subunits, rapsyn, agrin, MuSK, Dok-7, plectirn, and GFPT1 lead to endplate AChR deficiency. Third, collagen Q (ColQ) anchors acetylcholinesterase (AChE) to the synaptic basal lamina and mutations in COLQ lead to endplate AChE deficiency. By exploiting the synaptic basal lamina-targeting signal of ColQ, we recently reported that the exogenously administered AChE/ColQ complex can be specifically localized to the NMJ. The protein-anchoring therapy can be potentially applicable to a wide spectrum of defective extracellular matrix molecules. Fourth, CMS associated with episodic apnea is caused by mutations in choline acetyltransferase (ChAT) and skeletal muscle voltage-gated sodium channel (NaV1.4). In the past two years, we diagnosed 15 cases with CMS in Japan, and identified mutations in 12 patients. All the mutations except for one are unique to Japanese patients. We assume that more CMS cases still remain undiagnosed in Japan.
Full Text of this Article in Japanese PDF (236K)

(臨床神経, 52:1159−1161, 2012)
key words:神経筋接合部,先天性筋無力症候群,アセチルコリン受容体,アセチルコリンエステラーゼ,コラーゲンQ

(受付日:2012年5月24日)