Study of cerebellum disturbance by genetic approaches

2017 Fiscal Year Final Research Report

• Project/Area Number: 26242085
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Hiroshima University
• Principal Investigator: Kawakami Hideshi 広島大学, 原爆放射線医科学研究所, 教授 (70253060)
• Co-Investigator(Kenkyū-buntansha): 森野 豊之 広島大学, 原爆放射線医科学研究所, 准教授 (10397953) ; 大澤 亮介 広島大学, 原爆放射線医科学研究所, 助教 (20719356) ; 福士 雅也 広島大学, 医歯薬保健学研究科(医), 助教 (50313515) ; 山本 卓 広島大学, 理学研究科, 教授 (90244102) ; 丸山 博文 広島大学, 医歯薬保健学研究科(医), 教授 (90304443) ; 外丸 祐介 広島大学, 自然科学研究支援開発センター, 教授 (90309352) ; 平木 啓子 広島大学, 原爆放射線医科学研究所, 研究員 (10455397)
• Project Period (FY): 2014-06-27 – 2018-03-31
• Keywords: 脊髄小脳変性症 / Ca チャンネル

Outline of Final Research Achievements

We analyzed two Japanese families with autosomal dominant SCA using linkage analysis and exome sequencing, and identified CACNA1G, which encodes the calcium channel CaV3.1, as a new causative gene. Although most patients exhibited the pure form of cerebellar ataxia, two patients showed prominent resting tremor in addition to ataxia. CaV3.1 is classified as a low-threshold voltage-dependent calcium channel (T-type) . The mutation p.Arg1715His, identified in this study, was found to be located at S4 of repeat IV, the voltage sensor of the CaV3.1. Electrophysiological analyses revealed that the membrane potential dependency of the mutant CaV3.1 transfected into HEK293T cells shifted toward a positive potential
Our study also identifies Twinkle mutations as a cause of Perrault syndrome accompanied by neurologic features and expands the phenotypic spectrum of recessive disease caused by mutations in Twinkle.

Free Research Field

神経内科学