Genomic strategy identifies a missense mutation in WD-repeat domain 65 (WDR65) in an individual with Van der Woude syndrome.
Genomic strategy identifies a missense mutation in WD-repeat domain 65 (WDR65) in an individual with Van der Woude syndrome.
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DOI：
10.1002/ajmg.a.33980
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发表时间：
2011-06
影响因子：
2
通讯作者：
Schutte, Brian C.
中科院分区：
文献类型：
--
作者：
Rorick, Nicholas K.;Kinoshita, Akira;Weirather, Jason L.;Peyrard-Janvid, Myriam;Ferreira de Lima, Renata L. L.;Dunnwald, Martine;Shanske, Alan L.;Moretti-Ferreira, Danilo;Koillinen, Hannele;Kere, Juha;Mansilla, Maria A.;Murray, Jeffrey C.;Goudy, Steve L.;Schutte, Brian C.
关键词：
转录因子干扰素调节因子 6 (IRF6) 的遗传变异会导致口腔开裂疾病并增加其风险。我们假设 IRF6 调节的基因也与口腔裂隙疾病有关。我们使用五个标准来识别潜在的 IRF6 靶基因；取自野生型和 Irf6 缺陷小鼠胚胎的皮肤中基因表达存在差异，定位于 1p36-1p32 的范德沃德综合征 2 (VWS2) 位点，与 Irf6 重叠表达，启动子区域存在保守的预测结合位点，以及与 Irf6 突变小鼠相似的突变小鼠表型。此前，我们观察到 573 个基因的表达发生改变； 13 个位于与 VWS2 基因座同线的小鼠区域。其中两个基因 Wdr65 和 Stratifin 满足五个标准中的四个。 Wdr65 是一个新基因，编码预测的 1250 个氨基酸的蛋白质，具有两个 WD 结构域。作为 Irf6 调节的潜在靶标，我们假设在患有 VWS 或 VWS 样综合征的个体中，WDR65 和 Stratifin 中会发现致病突变。我们在一名 IRF6 没有外显子突变的 VWS 患者中发现了 WDR65 的潜在病因错义突变。表达和突变数据与 WDR65 是一种与口腔裂相关的新基因的假设一致。
Genetic variation in the transcription factor Interferon Regulatory Factor 6 (IRF6) causes and contributes risk for oral clefting disorders. We hypothesized that genes regulated by IRF6 are also involved in oral clefting disorders. We used five criteria to identify potential IRF6 target genes; differential gene expression in skin taken from wild type and Irf6-deficient murine embryos, localization to the Van der Woude syndrome 2 (VWS2) locus at 1p36–1p32, overlapping expression with Irf6, presence of a conserved predicted binding site in the promoter region, and a mutant murine phenotype that was similar to the Irf6 mutant mouse. Previously, we observed altered expression for 573 genes; 13 were located in the murine region syntenic to the VWS2 locus. Two of these genes, Wdr65 and Stratifin, met four of five criteria. Wdr65 was a novel gene that encoded a predicted protein of 1250 amino acids with two WD domains. As potential targets for Irf6 regulation, we hypothesized that disease-causing mutations will be found in WDR65 and Stratifin in individuals with VWS or VWS-like syndromes. We identified a potentially etiologic missense mutation in WDR65 in a person with VWS who does not have an exonic mutation in IRF6. The expression and mutation data were consistent with the hypothesis that WDR65 was a novel gene involved in oral clefting.
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影响因子：
2.6
作者：
Goudy, Steven;Law, Amy;Brown, Christopher
通讯作者：
Brown, Christopher
影响因子：
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作者：
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影响因子：
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作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
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作者：
Koillinen, H;Wong, FK;Kere, J
通讯作者：
Kere, J
影响因子：
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作者：
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通讯作者：
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