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

Moyamoya病(MMD)是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变。进行了全基因组关联研究，结果发现染色体17q25-ter与MMD风险有很强的关联。RNF213位点单倍型由7个SNP组成，与MMD密切相关(P=5.3×10-10)。RNF213基因突变分析显示，73%的非家族性MM患者和1.4%的对照组存在创始人突变p.R4859K，该突变极大地增加了MM的风险(P=1.2x10-43，优势比=190.8)。我们利用竞争等位基因特异性短寡核苷酸杂交(CASSOH)建立了这种方正基因突变的基因检测方法。CASSOH方法使我们能够在没有专家的情况下用免疫层析技术检测目标突变，这将有助于床边和临床上评估MMD的风险。

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.