PDGFRa mutations in humans with isolated cleft palate
PDGFRa mutations in humans with isolated cleft palate
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DOI：
10.1038/ejhg.2012.55
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发表时间：
2012-10-01
影响因子：
5.2
通讯作者：
Shotelersuk, Vorasuk
中科院分区：
文献类型：
--
作者：
Rattanasopha, Sawitree;Tongkobpetch, Siraprapa;Shotelersuk, Vorasuk
孤立性腭裂(CP)在人类中很常见，有复杂的遗传病因。已发现许多基因与脑瘫有关，但全谱基因仍不清楚。对血小板衍生生长因子受体α的全部编码区和30个非翻译区和微核糖核糖核酸(MiR)的全部编码区和30个非翻译区进行测序后，miR-140在9/102名CP患者的PDGFRA中发现了7个新的单碱基替换(8.8%)，而在5/500名种族匹配的未受影响的对照组中(1%)(双尾P值为0.0001)。其中4例为编码区错义突变，3例为3‘非编码区错义突变。4种改变(3种发生在编码，1种发生在3‘非编码区)与对照组相比差异有统计学意义(P<0.05)。1/102例患者和0/500例对照中发现了c*34G>；A。该位置在灵长类动物中保守，距离miR-140的预测结合位点有10bp的距离。荧光素酶分析表明，在miR-140存在的情况下，与野生型相比，c*34G>；A显著抑制了荧光素酶的活性，表明该变异体具有功能意义。这是第一个提供证据支持PDGFRA在人类CP中的作用的研究。《欧洲人类遗传学杂志》(2012年)2010581062；DOI：10.1038/ejhg.2012.55；2012年4月4日在线发布
Isolated cleft palate (CP) is common in humans and has complex genetic etiologies. Many genes have been found to contribute to CP, but the full spectrum of genes remains unknown. PCR-sequencing of the entire coding regions and the 30 untranslated region (UTR) of the platelet-derived growth factor receptor alpha (PDGFRa) and the microRNA (miR), miR-140 identified seven novel single base-pair substitutions in the PDGFRa in 9/102 patients with CP (8.8%), compared with 5/500 ethnic-matched unaffected controls (1%) (the two-tailed P-value < 0.0001). Of these seven, four were missense mutations in the coding regions and three in the 3'UTR. Frequencies of four changes (three in coding, one in 3'UTR) were statistically different from those of controls (P-value < 0.05). The c.*34G > A was identified in 1/102 cases and 0/500 controls. This position is conserved in primates and located 10 bp away from a predicted binding site for the miR-140. Luciferase assay revealed that, in the presence of miR-140, the c.*34G > A significantly repressed luciferase activity compared with that of the wild type, suggesting functional significance of this variant. This is the first study providing evidence supporting a role of PDGFRa in human CP. European Journal of Human Genetics (2012) 20, 1058-1062; doi: 10.1038/ejhg.2012.55; published online 4 April 2012