X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions
X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions
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DOI：
10.1038/ng0598-32
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发表时间：
1998-05-01
期刊：
影响因子：
30.8
通讯作者：
Dokal, I
中科院分区：
文献类型：
--
作者：
Heiss, NS;Knight, SW;Dokal, I
X连锁隐性遗传性先天性角化不良（DKC）是一种与Xq28相关的罕见骨髓衰竭疾病。用28个候选cDNA进行杂交筛选，结果用cDNA探针（来源于XAP 101）检测到1例DKC患者的3'缺失。随后在5名无关患者中发现了5种不同的错义突变，表明XAP 101是导致X连锁DKC（DKC 1）的基因。DKC 1跨越物种障碍高度保守，是大鼠NAP 57和酿酒酵母CBF 5的直系同源物。肽dyskerin含有两个TruB假尿苷（psi）合酶基序，多个磷酸化位点，和一个羧基末端赖氨酸丰富的重复结构域。通过类比已知dyskerin直向同源物的功能，预测该蛋白质参与细胞周期和核仁功能。
X-linked recessive dyskeratosis congenita (DKC) is a rare bone-marrow failure disorder linked to Xq28. Hybridization screening with 28 candidate cDNAs resulted in the detection of a 3' deletion in one DKC patient with a cDNA probe (derived from XAP101). Five different missense mutations in five unrelated patients were subsequently identified in XAP101, indicating that it is the gene responsible for X-linked DKC (DKC1). DKC1 is highly conserved across species barriers and is the orthologue of rat NAP57 and Saccharomyces cerevisiae CBF5. The peptide dyskerin contains two TruB pseudouridine (psi) synthase motifs, multiple phosphorylation sites, and a carboxy-terminal lysine-rich repeat domain. By analogy to the function of the known dyskerin orthologues, involvement in the cell cycle and nucleolar function is predicted for the protein.