2例色素失调症患儿的临床特征及遗传学分析

Clinical characteristics and genetic analysis of two children with incontinentia pigmenti

目的分析讨论色素失调症患儿(IP)临床表现及遗传学特征,以期提高对该病的认识与诊断。方法回顾性分析甘肃省妇幼保健院2例IP患儿的临床资料;利用Trio-全外显子测序(WES)和gap-PCR及Sanger测序,对患儿(先证者)IKBKG基因进行重排和点突变分析。结果病例1患儿重排结果为阴性,后续以全外显子组测序(WES)检测加Sanger测序验证,证实为IKBKG基因存在杂合变异:[chrX:153788622-153788623,c.519_c.520insCAGG,p.A174fs~*15]杂合突变;病例2患儿为IKBKG基因发生了重排。结论IP主要是染色体重排造成IKBKG基因失活所致,但本研究中的一例患儿重排检测结果为阴性。因此,对于临床症状高度疑似IP的患者,若gap-PCR结果为阴性,应同时加做WES等检测手段,以避免漏筛其余突变类型,如点突变、微重复和缺失等。综上,临床指征与基因测序技术相结合才是确诊IP的最佳方式。

Objective An analysis and discussion of the clinical manifestations and genetic characteristics of children with incontinentia pigmenti(IP)were conducted to enhance the understanding and diagnosis of this disease.Methods Involved a retrospective analysis of clinical data from two IP children at Gansu Provincial Maternity and Child-care Hospital.Furthermore,rearrangement and point mutation analysis of the IKBKG gene in the affected children(proband)were performed using Trio-whole exome sequencing(WES),gap-PCR,and Sanger sequencing.Results It indicated that the first case child initially tested negative for rearrangement,later confirmed to have a heterozygous variant in the IKBKG gene through WES and Sanger sequencing validation[chrX:153788622-153788623,c.519_c.520insCAGG,p.A174fs~*15]as a heterozygous mutation,while the second case child exhibited a rearrangement in the IKBKG gene.Conclusion It drawn was that incontinentia pigmenti(IP)is primarily caused by chromosomal rearrangements resulting in the inactivation of the IKBKG gene.However,one case in this study tested negative for rearrangement.Therefore,for patients displaying clinical symptoms highly suggestive of IP,if gap-PCR results are negative,additional testing methods such as WES should be conducted to avoid overlooking other mutation types like point mutations,micro-duplications,and deletions.In summary,the most effective approach to diagnosing IP involves a combination of clinical indications and first-line sequencing technologies.