一例X连锁隐性遗传的无汗型外胚层发育不良胎儿的产前遗传学诊断

Prenatal diagnosis of a fetus with X-linked hypohidrotic ectodermal dysplasia

目的对1例产前超声提示牙胚完全缺失疑为X-连锁无汗型外胚层发育不良胎儿及其母亲进行EDA基因变异分析,为产前诊断和遗传咨询提供依据。方法采集母亲的临床资料及血样,提取基因组DNA,扩增产物纯化后NGS测序,变异位点再进行Sanger测序验证,在胎儿的羊水细胞中采用Sanger测序验证同一位点。结果母亲的EDA基因第8外显子检测到c.574G>A杂合错义变异(p.Ala192Thr),胎儿为同一位点的半合子变异。根据变异类型及生物信息学软件预测可能均为致病性变异。结论EDA基因第8外显子的c.574G>A错义变异可能为该家系的致病性变异,结合临床资料符合X连锁隐性遗传规律,为产前诊断和遗传咨询提供依据。

Objective To detect variant of EDA gene in a fetus with absence of germ teeth detected by prenatal ultrasonography.Methods Clinical data and amniotic fluid and peripheral venous blood samples of the pregnant woman were collected for the analysis.Following extraction of genome DNA,the coding regions of the EDA gene were amplified by PCR and subjected to next-generation sequencing.Candidate variant was verified by Sanger sequencing.Results The pregnant woman was found to carry a heterozygous c.574G>A variant in the EDA gene,for which the fetus was hemizygous.Bioinformatic analysis suggested the variant to be pathogenic.Conclusion Combined ultrasonographic and genetic findings suggested the fetus is affected with X-linked hypohidrotic ectodermal dysplasia due to pathogenic variant of the EDA gene.