A rare Asian founder polymorphism of Raptor may explain the high prevalence of Moyamoya disease among East Asians and its low prevalence among Caucasians

Abstract

The online version of this article (doi:10.1007/s12199-009-0116-7) contains supplementary material, which is available to authorized users.

Distribution of Moyamoya Disease Susceptibility Polymorphism p.R4810K in RNF213 in East and Southeast Asian Populations

“…Moyamoya disease occurs in approximately one of 300 carriers in Japan. 8) This discrepancy in the allele frequency between cases and controls in Chinese people might be attributable to selection bias in the general populations in the previous study. 9) The primary aim of the present study was to estimate the population susceptible to moyamoya disease by conducting large scale screening for p.R4810K in general populations in East and Southeast Asia.…”

“…The estimated total numbers of carriers were 11.41 million for the Chinese, 1.36 million for the Korean, and 3.39 million for the Japanese populations. Assuming that moyamoya disease occurs in one of 300 carriers with p.R4810K, 8,9) the estimated numbers of patients with moyamoya disease attributable to p.R4810K are 38,000 in the Chinese, 4,500 in the Korean, and 11,300 in the Japanese populations. Although these numbers are very approximate and minimum estimates, because only the p.R4810K variant is considered, the large number of potential sufferers suggests that more attention should be paid to moyamoya disease in East Asian countries.…”

“…Specific factor(s) other than the genetic factor are needed to explain the variations in the clinical phenotypes and low penetrance among carriers. 8,9) Therefore, unknown modifier factor(s) may also be contributory to the differences in the clinical phenotypes. Further research is needed to identify such factor(s), which may also be crucial for the development of moyamoya disease among carriers of variant p.R4810K in RNF213.…”

“…2,7,10) We previously identified a susceptibility locus for familial moyamoya disease on 17q25.3. 11) Significant associations with genes in this region had been reported, 4,8) but rigorous identification had not been determined. The ring finger 213 (RNF213) gene was finally identified as a susceptibility gene for moyamoya disease by the conventional rigorous positional cloning approach, exome analysis, and functional analysis using zebrafish.…”

Review of Past Research and Current Concepts on the Etiology of Moyamoya Disease

“…From these view points, several studies have been conducted by using a combination of several methods to specify the susceptibility gene for moyamoya disease (Table 6). 29,38,39,43,47) Of these, two independent groups from Japan have identified, very recently, the susceptibility gene for moyamoya disease by employing a combination of several methods, including linkage analysis, case-control association studies, and gene annotation studies. Thus, Kamada and colleagues from Tohoku University employed a genome-wide association study and identified ring finger protein (RNF) 213 ( * 613768; http://omim.org/entry/613768) as the first moyamoya disease gene.…”