Development of a genetic test to evaluate the risk for Moyamoya disease

开发评估烟雾病风险的基因测试

• 批准号: 23659512
• 负责人: KURE Shigeo
• 金额: $ 2.41万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659512/
• 关键词: モヤモヤ病; 発症機序; 遺伝子検査; 遺伝子診断

Moyamoya disease (MMD) shows progressive cerebral angiopathy characterized by bilateral internal carotid artery stenosis and abnormal collateral vessels. A genome-wide association study was performed, which resulted in a strong association of chromosome17q25-ter with MMD risk. A single haplotype consisting of seven SNPs at the RNF213 locuswas tightly associated with MMD (P=5.3x10-10). Mutational analysis of RNF213 revealed a founder mutation, p.R4859K, in 73% of non-familial MMD cases and 1.4% of controls; this mutation greatly increases the risk of MMD (P=1.2x10-43, odds ratio=190.8). We developed a genetic testing method for this founder mutation by using CASSOH (competitive allele-specific short oligonucleotide hybridization). The CASSOH method enables us to detect the target mutation with immunechromatography without expertize, which would be useful for evaluation of a risk for MMD risk in bedside and clinic.

烟雾病（MMD）是一种以双侧颈内动脉狭窄和异常侧支血管为特征的进行性脑血管病。进行了全基因组关联研究，结果发现染色体17 q25-ter与MMD风险有很强的关联。RNF 213位点的7个SNPs组成的单倍型与MMD密切相关（P= 5.3 × 10 -10）。RNF 213的突变分析显示，在73%的非家族性MMD病例和1.4%的对照中存在创始突变p.R4859K;该突变大大增加了MMD的风险（P=1.2x10-43，比值比=190.8）。我们开发了一种基因检测方法，通过使用CASSOH（竞争等位基因特异性短寡核苷酸杂交）。CASSOH方法使我们能够在没有专业知识的情况下用免疫层析法检测靶点突变，这将有助于在床边和临床上评估MMD的风险。

项目成果

Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia

非酮症高甘氨酸血症患者服用丙戊酸钠后癫痫发作频率反而增加

• DOI: 10.1016/j.braindev.2011.01.005
• 发表时间: 2012
• 期刊: Brain Dev
• 作者: Morita M;Kuba K;Ichikawa A;Nakayama M;Katahira J;Iwamoto R;Watanebe T;Sakabe S;Daidoji T;Nakamura S;Kadowaki A;Ohto T;Nakanishi H;Taguchi R;Nakaya T;Murakami M;Yoneda Y;Arai H;Kawaoka Y;Penninger JM;Arita M;Imai Y.;Tsuyusaki Y
• 通讯作者: Tsuyusaki Y

Homozygous c. 14576G> A variant of RNF213 predicts early-onset and severe form of moyamoya disease

纯合子 C.

• 发表时间: 2012
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Shimojima K;他24名
• 通讯作者: 他24名

Identification of Moyamoya disease gene

烟雾病基因鉴定

• 发表时间: 2011
• 作者: Takayama N;Eto K;Kure S
• 通讯作者: Kure S

Identification of Moyamoya disease gene and its clinical significance

烟雾病基因鉴定及其临床意义

• 发表时间: 2012
• 作者: Wakabayashi Y;et al;Kure S
• 通讯作者: Kure S

モヤモヤ病遺伝子を追う特別講演

烟雾病基因专题讲座

• 发表时间: 2012
• 作者: Niihori T;Ihara K;他22名;Tojo Nakayama;呉繁夫
• 通讯作者: 呉繁夫