Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25

Background and Purpose-Moyamoya disease is a cerebrovascular disease of unk nown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoy a disease are occasionally seen in neurofibromatosis type I, of which the c ausative gene (NF1) has been assigned to chromosome 17q11.2. Methods-To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 famili es containing 56 patients with moyamoya disease, Leukocyte DNA extracted fr om the family members was subjected to polymerase chain reaction for a tota l of 22 microsatellite markers on chromosome 17. The amplified polymerase c hain reaction fragments were analyzed with GeneScan on an automated sequenc er. Results-Two-point linkage analysis gave a maximum log,, odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939 . The affected pedigree member method also showed a significantly low P val ue (<1.0X10(-5)) far the 5 adjacent markers at 17q25. Multipoint linkage an alysis also indicated that the disease gene is contained within the 9-cM re gion of D17S785 to D17S836, with a maximum LOD score of 4.58. Conclusions-A gene for familial moyamoya disease is located on chromosome 1 7q25.