Matsumine H, Saito M, Shimoda-Matsubayashi S, Tanaka H, Ishikawa A, Nakagawa-Hattori Y, Yokochi M, Kobayashi T, Igarashi S, Takano H, Sanpei K, Koike R, Mori H, Kondo T, Mizutani Y, Schäffer A A, Yamamura Y, Nakamura S, Kuzuhara S, Tsuji S, Mizuno Y
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
Am J Hum Genet. 1997 Mar;60(3):588-96.
An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.
青少年帕金森病的常染色体隐性形式（AR-JP）（MIM 600116）是一种对左旋多巴有反应的帕金森病，其病理表现为黑质致密部多巴胺能神经元的高度选择性退化。通过对锰超氧化物歧化酶基因（SOD2）双等位基因多态性的连锁分析，我们发现一个患有AR-JP的家系，该疾病与SOD2基因座表现出完美的分离。通过将连锁分析扩展到13个患有AR-JP的家系，我们发现了强有力的证据，证明AR-JP基因定位于6号染色体的6q25.2-27区域，包括SOD2基因座，在D6S305（θ = 0.03）和D6S253（θ = 0.02）处的最大累积成对LOD分数分别为7.26和7.71。对必然重组事件的观察以及多点连锁分析将AR-JP基因定位在D6S437和D6S264之间17厘摩的区间内。确定AR-JP基因将是我们理解黑质神经元选择性退化潜在分子机制的重要一步。
