A promoter sequence variant of ZNF750 is linked with familial psoriasis
A promoter sequence variant of ZNF750 is linked with familial psoriasis
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DOI：
10.1038/jid.2008.1
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发表时间：
2008-07-01
影响因子：
6.5
通讯作者：
Chen, Yuan-Tsong
中科院分区：
文献类型：
--
作者：
Yang, Chi-Fan;Hwu, Wuh-Liang;Chen, Yuan-Tsong
我们先前在一个五代常染色体显性银屑病中国家族中将银屑病易感基因定位到17 q末端的3.8 Mb区域。为了确定该家族中导致银屑病的突变，我们对该区域内的78个基因进行了测序，发现了4个基因变体，p.Ala201Val在CD 7中，c.锌指蛋白750（ZNF 750）的p.625A>C、C17 orf 56的p.Asp189Asn和AATK的p.Ala568Thr与该病共分离。在其他家族性银屑病中没有疾病分离并且在正常受试者中存在变体的情况下，未进一步研究后两种变体。CD 7的功能分析不支持CD 7作为致病基因。相比之下，C。ZNF 750中625 A>C突变导致启动子活性降低42%，电泳迁移率变动分析显示核蛋白与突变C等位基因结合。C.另1例散发性银屑病患者存在625 A>C突变，而188例正常对照均未发现该突变。总之，该突变占中国人群银屑病的1.7%（置信区间：0.2-5.84%）。这份报告表明，ZNF 750突变可能有助于银屑病的易感性。
We previously mapped a psoriasis-susceptibility gene to a 3.8-Mb region of the 17q terminus in a five-generation Chinese family with autosomal-dominant psoriasis. To identify the mutations responsible for the psoriasis in this family, we sequenced 78 genes within the region and found four gene variants, p.Ala201Val in CD7, c.-625A>C in zinc-finger protein 750 (ZNF750), p.Asp189Asn in C17orf56, and p.Ala568Thr in AATK cosegregated with the disease. The latter two variants were not studied further in the absence of disease segregation in other familial psoriasis and presence of variants in normal subjects. Functional analyses of CD7 did not support CD7 as a disease-causing gene. In contrast, the c.-625A>C mutation in ZNF750 resulted in a 42% reduction of the promoter activity, and the electrophoretic mobility shift assay showed binding of nuclear protein(s) to the mutant C allele. The c.-625A>C mutation was found in another sporadic psoriasis patient but was absent in 188 normal controls. Together, the mutation accounts for 1.7% (confidence interval: 0.2-5.84%) of psoriasis in the Chinese population. This report suggests that ZNF750 mutations could contribute to psoriasis susceptibility.