胎儿全外显子测序在非免疫性胎儿水肿病因评估及预后中的应用

Utility of fetal whole exome sequencing in the etiological evaluation and outcome of nonimmune hydrops fetalis.

作者信息

Correa Alec Reginald Errol, Naini Kamal, Mishra Pallavi, Dadhwal Vatsla, Agarwal Ramesh, Shukla Rashmi, Kabra Madhulika, Gupta Neerja

机构信息

Department of Pediatrics, Division of Genetics, All India Institute of Medical Sciences, New Delhi, India.

Department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Prenat Diagn. 2021 Oct;41(11):1414-1424. doi: 10.1002/pd.6022. Epub 2021 Aug 2.

DOI:10.1002/pd.6022

PMID:34302381

Abstract

INTRODUCTION

Nonimmune hydrops fetalis (NIHF) has varied etiology. We assessed the etiological spectrum and evaluated the utility of fetal whole exome sequencing (fWES) for the diagnosis of NIHF.

METHODS

In this prospective cohort study, we evaluated antenatally diagnosed fetuses with NIHF between July 2018 and December 2019 according to the routine diagnostic algorithm. Fetuses that remained undiagnosed after routine NIHF workup were subjected to fetal chromosomal microarray and/or WES. Pregnancies were followed up for clinical outcomes.

RESULTS

Of the 45 fetuses, consanguinity and recurrent hydrops fetalis were observed in 13.3% (6/45) and 28.8% (13/45), respectively. Overall, an etiological diagnosis was possible in 75.5% (34/45) of fetuses, while the cause remained unknown in 24.4% (11/45). A genetic etiology was identified in 46.6% (21/45): aneuploidy and monogenic disorders in 28.8% (13/45) and 17.8% (8/45), respectively. fWES on 19 fetuses detected disease-causing variants in 42.1% (8/19). Nine novel variants were detected in RAPSN, ASCC1, NEB, PKD1L1, GUSB, and PIEZO1. Only 8.8% (4/45) of the cohort survived without morbidity.

CONCLUSIONS

This study describes the etiological spectrum and the disease-causing variants in an Indian cohort of hydropic fetuses.

摘要

引言

非免疫性胎儿水肿（NIHF）病因多样。我们评估了病因谱，并评估了胎儿全外显子测序（fWES）在NIHF诊断中的效用。

方法

在这项前瞻性队列研究中，我们根据常规诊断算法对2018年7月至2019年12月期间产前诊断为NIHF的胎儿进行了评估。常规NIHF检查后仍未确诊的胎儿接受了胎儿染色体微阵列和/或WES检查。对妊娠进行临床结局随访。

结果

45例胎儿中，分别有13.3%（6/45）和28.8%（13/45）观察到近亲结婚和复发性胎儿水肿。总体而言，75.5%（34/45）的胎儿可以做出病因诊断，而24.4%（11/45）的病因仍不清楚。46.6%（21/45）的胎儿确定了遗传病因：非整倍体和单基因疾病分别占28.8%（13/45）和17.8%（8/45）。对19例胎儿进行fWES检测，42.1%（8/19）检测到致病变异。在RAPSN、ASCC1、NEB、PKD1L1、GUSB和PIEZO1中检测到9个新变异。该队列中只有8.8%（4/45）的胎儿存活且无发病。