The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1.
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.
Greer
W L
WL
Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia. wgreer@IS.Dal.ca
Riddell
D C
DC
Gillan
T L
TL
Girouard
G S
GS
Sparrow
S M
SM
Byers
D M
DM
Dobson
M J
MJ
Neumann
P E
PE
D000483:Alleles; D002352:Carrier Proteins; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016464:Lysosomal Storage Diseases / Q000235:genetics; D008562:Membrane Glycoproteins; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000145:classification / Q000235:genetics*; D009674:Nova Scotia; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins