NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C

Hum Genet. Jul-Aug 1999;105(1-2):10-6. doi: 10.1007/s004399900059.


Complementary and genomic DNAs isolated from the fibroblasts of 10 Japanese (7 late infantile, 2 juvenile, and 1 adult form of the disease) and one Caucasian patient with Niemann-Pick disease type C were analyzed for mutations in the NPC1 gene. Fourteen novel mutations were found including small deletions and point mutations. A one-base deletion and a point mutation caused splicing errors. The mutations were not clustered in any particular region of the gene and were found both in and out of the transmembrane domains. Three patients were homozygous, five were compound heterozygous, and the remaining three were suspected of being compound hetrozygous with an unknown error in one of their NPC1 alleles. Of the 14 mutations, the G1553A substitution that caused a splicing error of exon 9 appeared to be relatively common in Japanese patients, because two patients were homozygous and one patient was compound heterozygous for this mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alternative Splicing
  • Blotting, Southern
  • Carrier Proteins*
  • Cell Line
  • Child
  • Child, Preschool
  • DNA, Complementary / analysis
  • Exons
  • Female
  • Gene Deletion
  • Genotype
  • Humans
  • Japan
  • Male
  • Membrane Glycoproteins*
  • Models, Genetic
  • Mutation*
  • Mutation, Missense
  • Niemann-Pick Diseases / genetics*
  • Phenotype
  • Point Mutation
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Carrier Proteins
  • DNA, Complementary
  • Membrane Glycoproteins
  • NPC1 protein, human
  • Proteins