LIMITING THE NIEMANN-PICK TYPE-C CRITICAL REGION TO A 1-CM INTERVAL

Objective: To refine the position of and isolate the gene responsible for Niemann-Pick Type II (NP Type II) disease, an autosomal, recessive neurodegenerative disorder usually affecting children. The underlying biochemical defect results in an impairment in transport of intracell ular cholesterol. This disease has been classified into two subtypes, NPC and NPD. NPD and the major complementation group of NPC both map t o chromosome 18q11-12; therefore, they are likely allelic variants. Th e NP Type II gene was previously localized between microsatellite mark ers D18S44 and D18S1108. Design: Linkage analysis. Setting: Pathology department of a university-associated hospital. Patients: An NPC famil y, including proband, parents and sister. Outcome measures: NP Type II disease phenotype and biochemical phenotype (cholesterol esterificati on). Results: DNA from the individuals in the NPC family was genotyped at 12 microsatellite loci from the critical region. The deduced haplo types identify a meiotic recombinant that has allowed the distal Limit of the critical region to be moved from D18S1108 to D18S1101. Conclus ion: The NP Type II gene lies proximal to the microsatellite marker D1 8S1101, within the 1-cM interval between D18S1101 and D18S1398. This r epresents approximately 1.1 mb on the physical map.