全外显子组测序检测先天性外胚层发育不良一例及家系分析

Genetic analysis of a case with ectodermal dysplasia using whole exome sequencing

目的对1例反复高热疑似为少汗型外胚层发育不良的患儿进行基因检测,以明确其病因。方法应用医学全外显子组测序技术(whole exome sequencing,WES)检测患者基因组内的单核苷酸变异,用低深度全基因组测序技术(low-coverage massively parallel copy number variation sequencing,CNV-seq)对WES检测的结果进行验证,应用PCR和实时荧光定量PCR技术检测患者及母亲EDA基因第3~8外显子的缺失情况。结果WES检测提示患儿chrX:69243016-69395730区可能存在半合子缺失。CNV-seq检测提示患儿Xq13.1区存在约0.12 Mb的缺失,缺失范围涉及EDA基因。PCR检测确认患儿EDA基因第3~8外显子存在半合子缺失,其母亲未见相同缺失。结论患儿为EDA基因第3~8外显子半合子缺失变异所致的少汗型外胚层发育不良患者,可能为新发变异或其母亲为生殖腺嵌合体。WES和CNV-seq技术对于诊断罕见疾病中具有较高的价值。

Objective To explore the genetic cause of a patient suspected for congenital ectodermal dysplasia with repeated hyperthermia and to assess the reproductive risk for his family.Methods Medical whole-exome sequencing(WES)were used to detect single-nucleotide variations and low-coverage massively parallel copy number variation sequencing(CNV-seq)were employed to verify suspected CNVs.PCR and real-time quantitative PCR were applied to confirm the deletion of EDA gene.Results The results of WES suggested that the patient carried a hemizygous deletion for chrX:69243016-69395730.CNV-seq indicated that the patient carried a deletion of approximately 0.12 Mb on Xq13.1,which encompassed the EDA gene.The PCR results confirmed that there was a hemizygous deletion of exons 3 to 8 of the EDA gene.The same deletion was not found in his mother.Conclusion The congenital ectodermal dysplasia of the patient may be attributed to deletion of exons 3 to 8 of the EDA gene,which could be de novo or derive from germline mosaicism of his mother.The WES and CNV-seq are of great value for the diagnosis of rare diseases.