Morris J A, Zhang D, Coleman K G, Nagle J, Pentchev P G, Carstea E D
National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland, 20892, USA.
Biochem Biophys Res Commun. 1999 Aug 2;261(2):493-8. doi: 10.1006/bbrc.1999.1070.
Niemann-Pick C (NP-C) is a fatal autosomal recessive storage disorder characterized by progressive neurodegeneration and variable hepatosplenomegaly. At the cellular level, cells derived from an affected individual accumulate unesterified cholesterol in lysosomes when cultured with low-density lipoprotein. The NP-C gene was identified at 18q11. The transcript is 4.9 kb encoding a 1278-amino-acid protein. We have defined the genomic structure of NPC1 along with the 5' flanking sequence. The NPC1 gene spans greater than 47 kb and contains 25 exons. Exons range in size from 74 to 788 bp with introns ranging in size from 0.097 to 7 kb. All intron/exon boundaries follow the GT/AG rule. The 5' flanking sequence has a CpG island containing multiple Sp1 sites indicative of a promoter region. The CpG island is located in the 5' flanking sequence, exon 1 and the 5' end of intron 1. We have also identified multiple single nucleotide polymorphisms in the coding and intronic sequences.
尼曼-匹克C型（NP-C）病是一种致命的常染色体隐性贮积病，其特征为进行性神经退行性变和不同程度的肝脾肿大。在细胞水平上，来自患病个体的细胞在与低密度脂蛋白一起培养时，会在溶酶体中积累未酯化的胆固醇。NP-C基因定位于18q11。该转录本为4.9 kb，编码一个含1278个氨基酸的蛋白质。我们已经确定了NPC1的基因组结构以及5'侧翼序列。NPC1基因跨度超过47 kb，包含25个外显子。外显子大小从74到788 bp不等，内含子大小从0.097到7 kb不等。所有内含子/外显子边界均遵循GT/AG规则。5'侧翼序列有一个CpG岛，含有多个Sp1位点，提示为启动子区域。CpG岛位于5'侧翼序列、外显子1和内含子1的5'端。我们还在编码序列和内含子序列中鉴定出多个单核苷酸多态性。
