汉族非综合型唇腭裂患者家系中IFT88突变研究

A mutation in IFT88 in a Han Chinese pedigree with non-syndromic cleft lip and/or palate

目的:探索一个中国汉族非综合型唇腭裂家系的潜在致病基因。方法:对先证者及其有唇腭裂表型的父亲和无唇腭裂表型的母亲分别进行全外显子组测序。通过遗传模型、等位基因频率和文献回顾等筛选出该家系的潜在致病变异。利用Sanger测序和保守性分析对潜在致病变异的影响进行初步评价。结果:在该家系中发现并验证了位于IFT88的一个低频错义突变p.Arg750Lys(c.2249G>A),这是一个之前未曾报道过的新突变,在52个中国汉族健康对照的Sanger测序中也未发现该突变。该突变位点在物种进化中高度保守,提示可能对IFT88蛋白的结构和功能产生重要影响。结论:IFT88 p.Arg750Lys可能是该家系出现唇腭裂表型的潜在致病突变。该结果为IFT88是唇腭裂的致病基因进一步提供了证据。

Objective:To identify the causative gene mutation of a Han Chinese family with non-syndromic cleft lip and/or palate(NSCL/P).Methods:Whole-exome sequencing was conducted on the proband and his parents.The Mendelian inheritance model,allele frequencies and literature review were used to screen and filter the variants.Sanger sequencing and conservation analysis were conducted for preliminary evaluation.Results:A missense mutation c.2249G>A in the Intraflagellar transport 88(IFT88)gene predicting p.Arg750Lys was identified.The mutation was not reported in public databases and the result of Sanger sequencing in 52 Han Chinese healthy controls.The missense alteration affects an amino acid that is evolutionarily conserved in the IFT88 protein.Conclusions:Our findings suggest that the p.Arg750Lys mutation of IFT88 may be causative for this CL/P pedigree.Our results add to the evidence that IFT88 variants may play a role in the pathogenesis of orofacial clefts.