[Brief History of the Search for Susceptibility Loci for Moyamoya Disease].

Abstract

Here, I briefly describe the determination of locus 17q25 on chromosome 17 for a moyamoya disease susceptibility gene, focusing on our study. At the beginning of the study, linkage analysis was challenging. However, our efforts finally achieved statistically significant results at locus 17q25 with a logarithm of odds(LOD) score of 3.11, a maximum LOD score of 4.58, and p-value of 0.00001 with parametric linkage analysis, multipoint analysis, and nonparametric Affected Pedigree Member analysis, respectively. This was due to the good fortune of choosing chromosome 17 as the primary target, given that neurofibromatosis type 1 and moyamoya disease occur simultaneously in some cases. Moreover, our success was largely due to the contributions of our collaborators who precisely determined the disease traits and collected DNA(leukocyte) samples from 103 individuals from 24 families. After our publication in 2000, a research group from Kyoto University searched for the locus 17q25.3 and discovered a mutation in RNF213 gene. Simultaneously, a group from Tohoku University performed a genome-wide association study and determined RNF213 to be a susceptibility gene for moyamoya disease. This occurred 11 years after our first results.