BACKGROUND AND METHODS Syndactyly is a congenital disorder caused by an irregularity in limb formation during the embryonic development. Many studies have demonstrated the critical effect of genetic factor in controlling the outcome of non-syndromic syndactyly. However the signaling pathway causing this disease has not been fully understood. The aim of this study was to identify the genetic mutations that related to syndactyly type I-c and I-d by exome sequencing. RESULTS The exome sequence from two patients revealed two novel heterozygous missense mutations: GLI3: cG1622A pT541M and GJA1: cT274C p.Y92H. Sanger sequencing result confirmed that these mutations were present under heterozygous form in the affected mothers, but not in the unaffected fathers. In-silico analyses by SIFT, Polyphen-2, PredictSNP, PhD-SNP, and PROVEAN did confirm the damaging effect of these mutations in the structure and function of the proteins. CONCLUSIONS The result suggested that the two novel mutations may be pathogenic for the disease in these families under the dominant model, provided the initial data for further functional studies to investigate whether those mutations play a disturbing role in the molecular network of syndactyly.

中文翻译：

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通过整个外显子组测序鉴定与两个越南人中的非症状性综合征相关的新型错义突变。

背景和方法综合征是一种先天性疾病，由胚胎发育过程中肢体形成不规则引起。许多研究表明遗传因素在控制非综合症结局中的关键作用。然而，导致这种疾病的信号传导途径尚未完全被理解。这项研究的目的是通过外显子组测序鉴定与Syndylyly Ic和Id类型相关的基因突变。结果两名患者的外显子组序列显示了两个新的杂合错义突变：GLI3：cG1622A pT541M和GJA1：cT274C p.Y92H。桑格测序结果证实，这些突变以杂合子形式存在于受影响的母亲中，而不存在于未受影响的父亲中。通过SIFT，Polyphen-2，PredictSNP，PhD-SNP进行计算机内分析 PROVEAN确实证实了这些突变对蛋白质结构和功能的破坏作用。结论结果表明，在优势模型下，这两个新突变可能是这些家族中的致病原，为进一步的功能研究提供了初步数据，以研究这些突变是否在组织分子网络中发挥干扰作用。