The whole-exome sequencing of 68 Caucasian patients with moyamoya disease or moyamoya syndrome demonstrated that rare missense variants of RNF213 were associated with the development of moyamoya disease (odds ratio, 2.24); moreover, a hotspot of rare variants was identified for the 6.2kb C-terminal region near the RING-finger domain. This evidence concerns the gene RNF213 and Moyamoya disease.