Identification of novel mutations in the NPC1 gene in German patients with Niemann–Pick C disease
Identification of novel mutations in the NPC1 gene in German patients with Niemann–Pick C disease
复制标题
德国尼曼-皮克 C 病患者 NPC1 基因新突变的鉴定
DOI：
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发表时间：
2002
影响因子：
4.2
通讯作者：
Gerd Schmitz
中科院分区：
文献类型：
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作者：
Wolfgang E. Kaminski;H. Klünemann;Bernd Ibach;C. Aslanidis;Helmfried E. Klein;Gerd Schmitz
尼曼-皮克病C型（NPC）是一种与细胞内胆固醇转运缺陷相关的遗传性神经退行性疾病。两种不同基因NPC1和HE1的突变最近被证明会导致这种疾病。我们分析了来自四个不相关家族的5名德国鼻咽癌患者的NPC1基因。我们在NPC1基因的编码区共发现了5个新的突变（G231V、D874V、I642M、I1094T和R116stop）。所有受影响个体均表现为复合杂合性。突变的等位基因由未受影响的父母传播，除了一名患者发生了新生突变（G231V）。有趣的是，该个体的G231V/P237S NPC1基因型与早发型鼻咽癌相关。相反，我们发现在另一位鼻咽癌患者中观察到的D874V/D948N基因型的特点是临床症状晚发，表现为明显的白质疾病。我们的研究结果将有助于确定尼曼-匹克C病的临床表型和遗传异常之间的关系。
Niemann–Pick disease type C (NPC) is an inherited neuro degenerative disorder associated with intracellular cholesterol trafficking defects. Mutations in two distinct genes, NPC1 and HE1, have recently been shown to cause this disease. We have analysed the NPC1 gene in five German patients with NPC from four unrelated families. We identified a total of five novel mutations in the coding region of the NPC1 gene (G231V, D874V, I642M, I1094T and R116stop). All affected individuals displayed compound heterozygosity. The mutated alleles were transmitted by the nonaffected parents with the exception of one patient, in whom a de novo mutation (G231V) had occurred. Interestingly, the G231V/P237S NPC1 genotype in this individual is associated with an early-onset form of NPC. In contrast, we found that the D874V/D948N genotype, observed in another NPC patient, is characterized by a late onset of clinical symptoms that presents with a pronounced white-matter disease. Our results will contribute to defining the association between the clinical phenotypes and the genetic abnormalities in Niemann–Pick C disease.
影响因子：
56.9
作者：
Naureckiene, S;Sleat, DE;Lobel, P
通讯作者：
Lobel, P
影响因子：
56.9
作者：
Davies, JP;Chen, FW;Ioannou, YA
通讯作者：
Ioannou, YA