一例肾单位肾痨2型胎儿的产前超声表型及遗传学分析

Ultrasonographic manifestation and genetic analysis of a fetus with nephronophthisis type 2

目的对1例既往有胎儿双肾体积增大及羊水过少孕育史,本次妊娠16周余超声提示为双侧多囊性肾发育不良及羊水过少的引产胎儿行肾脏病理及分子遗传学检查,明确其病因,并为该家系的产前诊断和遗传咨询提供依据。方法对胎儿行超声检查明确其肾脏形态学改变,经遗传咨询后胎儿父母决定终止妊娠,取引产胎儿肾脏组织行病理学检查,通过目标区域捕获二代测序(next generation sequencing,NGS)对胎儿行遗传性肾脏疾病基因变异筛查,对胎儿及其父母行可疑致病基因变异位点Sanger测序验证。结果胎儿肾脏组织学检查提示为多囊性改变,未见正常的肾脏结构、肾皮质或髓质。NGS和PCR等检查明确胎儿携带INVS基因c.100+1G>A杂合变异和第3外显子杂合缺失,均为致病性变异,分别来自其母亲和父亲。结论对一个双侧多囊性肾发育不良引产胎儿明确诊断为肾单位肾痨2型(typeⅡnephronophthisis,NPHP2),对该家庭再次生育提供了精准的指导。NPHP2疾病的基因诊断在国内鲜有报道,本研究结果加强了对该类疾病临床表现和遗传学病因的认识。

Objective To carry out genetic analysis for a family with a fetus manifesting bilateral polycystic renal dysplasia and oligohydramnios at 16+gestational week and a previous history for fetal renal anomaly.Methods Ultrasound scan was carried out to detect the morphological changes.Following genetic counselling,the parents had decided to terminate the pregnancy.Fetal kidneys were subjected to histological examination.Target capture and next generation sequencing(NGS)was applied to the abortus to detect potential variants.The results were verified by Sanger sequencing.Results Histological examination of fetal kidneys revealed cystic changes without cortex,medulla or normal renal structure.NGS has identified a heterozygous c.100+1G>A variant and deletion of exon 3 of the INVS gene,which were respectively inherited from the mother and father.Conclusion Through NGS and Sanger sequencing,the fetus was diagnosed with typeⅡnephronophthisis(NPHP2).Above result can provide guidance for further pregnancy and enforce understanding of clinical features and genetic etiologies for NPHP.