Whole-exome sequencing in the evaluation of fetal congenital anomalies of the kidney and urinary tract detected by ultrasonography
Whole-exome sequencing in the evaluation of fetal congenital anomalies of the kidney and urinary tract detected by ultrasonography
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全外显子组测序评估超声检测胎儿肾脏和泌尿道先天性异常
DOI：
10.1002/pd.5737
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发表时间：
2020-07-15
影响因子：
3
通讯作者：
Liao, Can
中科院分区：
文献类型：
--
作者：
Lei, Ting-Ying;Fu, Fang;Liao, Can
目的 我们旨在研究全外显子组测序（WES）在患有肾及尿路先天性异常（CAKUT）且伴有或不伴有其他结构异常，但核型分析和染色体微阵列分析（CMA）结果正常的胎儿中的应用价值。方法 对患有CAKUT且伴有或不伴有其他结构异常的病例进行资格筛选。排除核型分析或CMA结果异常的胎儿。我们对符合条件的胎儿 - 父母三联体的DNA样本进行WES，并根据超声特征识别诊断性基因变异。结果 共有163个符合条件的胎儿 - 父母三联体通过WES成功分析。我们在20个胎儿的18个基因中发现了26个可能致病或致病性变异，诊断性基因变异的总比例为12.3%（20/163）。在患有多系统异常（27.0%，10/37）、肾脏增大/肾回声增强（20%，4/20）和多囊性发育不良肾（11.1%，4/36）的胎儿中，基因变异的检出频率显著更高。妊娠结局数据显示，WES结果为阴性的存活病例中，88例（94.6%，88/93）在幼儿早期预后良好。结论 我们的研究是产前应用WES对CAKUT进行研究中规模最大的一项，结果表明WES可用于诊断以明确不明原因CAKUT的分子缺陷。
Objective We aimed to investigate the value of whole-exome sequencing (WES) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with or without other structural anomalies but with normal findings upon karyotyping and chromosome microarray analysis (CMA). Methods Cases with CAKUT with or without other structural anomalies were screened for eligibility. Fetuses with abnormal karyotyping or CMA results were excluded. We performed WES on DNA samples from eligible fetus-parental trios and identified diagnostic genetic variants based on ultrasonographic features. Results A total of 163 eligible fetus-parental trios were successfully analyzed by WES. We found 26 likely pathogenic or pathogenic variants in 18 genes from 20 fetuses, with a total proportion of diagnostic genetic variants of 12.3% (20/163). Genetic variants were significantly more frequently detected in fetuses with multisystem anomalies (27.0%, 10/37), enlarged kidney/echogenic kidney (20%, 4/20), and multicystic dysplastic kidney (11.1%, 4/36). Pregnancy outcome data showed that 88 (94.6%, 88/93) of the surviving cases with negative WES results had a good prognosis in early childhood. Conclusions Our study is the largest to use WES prenatally for CAKUT and shows that WES can be used diagnostically to define the molecular defects that underlie unexplained CAKUT.