title: NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.
abstract: 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.
authors.affiliation: Gene Research Center, Tottori University, Yonago, Japan. tyamamot@grape.med.tottori-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: E
authors.initials: E
authors.lastname: Nanba
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: K
authors.initials: K
authors.lastname: Higaki
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Akaboshi
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Takeshima
authors.forename: K
authors.initials: K
authors.lastname: Inui
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Sakuragawa
authors.forename: G
authors.initials: G
authors.lastname: Millat
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
authors.forename: J A
authors.initials: JA
authors.lastname: Morris
authors.forename: P G
authors.initials: PG
authors.lastname: Pentchev
authors.forename: K
authors.initials: K
authors.lastname: Ohno
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D017398:Alternative Splicing; D015139:Blotting, Southern; D002352:Carrier Proteins; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins