THE NOVA-SCOTIA (TYPE-D) FORM OF NIEMANN-PICK-DISEASE IS CAUSED BY A G(3097)-]T TRANSVERSION IN NPC1

Niemann-Pick type D (NPD) disease is a progressive neurodegenerative d isorder characterized by the accumulation of tissue cholesterol and sp hingomyelin. This disorder is relatively common in southwestern Nova S cotia, because of a founder effect. Our previous studies, using classi c linkage analysis of this large extended kindred, defined the critica l gene region to a 13-cM chromosome segment between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is mutated in the ma jority of patients with Niemann-Pick type C disease. We have identifie d a point mutation within this gene (G3097-->T; Gly992-->Trp) that sho ws complete linkage disequilibrium with NPD, confirming that NPD is an allelic variant of NPC1.