LINKAGE OF NIEMANN-PICK-DISEASE TYPE-D TO THE SAME REGION OF HUMAN-CHROMOSOME-18 AS NIEMANN-PICK-DISEASE TYPE-C

Niemann-Pick type II disease is a severe disorder characterized by acc umulation of tissue cholesterol and sphingomyelin and by progressive d egeneration of the nervous system. This disease has two clinically sim ilar subtypes, type C (NPC) and type D (NPD). NPC is clinically variab le and has been identified in many ethnic groups. NPD, on the other ha nd, has been reported only in descendants of an Acadian couple who liv ed in Nova Scotia in the early 18th century and has a more homogeneous expression resembling that of less severely affected NPC patients. De spite biochemical differences, it has not been established whether NPC and NPD are allelic variants of the same disease. We report here that NPD is tightly linked (recombination fraction .00; maximum LOD score 4.50) to a microsatellite marker, D18S480, from the centromeric region of chromosome 18q, Carstea et al. have reported that the NPC gene map s to this same site; therefore we suggest that NPC acid NPD likely res ult from mutations in the same gene.