Greer W L, Riddell D C, Gillan T L, Girouard G S, Sparrow S M, Byers D M, Dobson M J, Neumann P E
Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia.
Am J Hum Genet. 1998 Jul;63(1):52-4. doi: 10.1086/301931.
Niemann-Pick type D (NPD) disease is a progressive neurodegenerative disorder characterized by the accumulation of tissue cholesterol and sphingomyelin. This disorder is relatively common in southwestern Nova Scotia, because of a founder effect. Our previous studies, using classic linkage analysis of this large extended kindred, defined the critical gene region to a 13-cM chromosome segment between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is mutated in the majority of patients with Niemann-Pick type C disease. We have identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows complete linkage disequilibrium with NPD, confirming that NPD is an allelic variant of NPC1.
尼曼-匹克D型（NPD）病是一种进行性神经退行性疾病，其特征是组织胆固醇和鞘磷脂积累。由于奠基者效应，这种疾病在新斯科舍省西南部相对常见。我们之前的研究通过对这个大型扩展家系进行经典连锁分析，将关键基因区域定位到D18S40和D18S66之间13厘摩的染色体区段。最近从该区域分离出的NPC1基因在大多数尼曼-匹克C型病患者中发生了突变。我们在该基因内鉴定出一个点突变（G3097→T；Gly992→Trp），它与NPD表现出完全连锁不平衡，证实NPD是NPC1的等位基因变体。
