Yamamoto T, Nanba E, Ninomiya H, Higaki K, Taniguchi M, Zhang H, Akaboshi S, Watanabe Y, Takeshima T, Inui K, Okada S, Tanaka A, Sakuragawa N, Millat G, Vanier M T, Morris J A, Pentchev P G, Ohno K
Gene Research Center, Tottori University, Yonago, Japan.
Hum Genet. 1999 Jul-Aug;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.
从10名日本尼曼-匹克病C型患者（7例晚婴儿型、2例青少年型和1例成人型）以及1名高加索患者的成纤维细胞中分离出互补DNA和基因组DNA，对NPC1基因的突变情况进行分析。发现了14种新突变，包括小缺失和点突变。一个单碱基缺失和一个点突变导致了剪接错误。这些突变并非聚集在基因的任何特定区域，在跨膜结构域内外均有发现。3例患者为纯合子，5例为复合杂合子，其余3例疑似为复合杂合子，其NPC1等位基因之一存在未知错误。在这14种突变中，导致外显子9剪接错误的G1553A替换在日本患者中似乎相对常见，因为有2例患者为此突变的纯合子，1例患者为此突变的复合杂合子。
