Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts

We analyzed Niemann-Pick type C disease 1 (NPC1) gene in 12 patients with Niemann-Pick type C dis- ease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound het- erozygotes. We found 15 mutations, eight of which previ- ously unreported. The comparison of cDNA and genomic DNA revealed discrepancies in some subjects. In two unre- lated patients carrying the same mutations (P474L and nt 2972del2) only one mutant allele (P474L), was expressed in fibroblasts. The mRNA corresponding to the other allele was not detected even in cells incubated with cyclohexi- mide. The promoter variants ( � 1026T/G and � 1186T/C or