Abstract
OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).
METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.
RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2 = 78%], 16% [95% CI, 6%-26%; I2 = 80%] and 51% [95% CI, 27%-75%; I2 = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).
CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.
| Original language | English |
|---|---|
| Pages (from-to) | 187-195 |
| Number of pages | 9 |
| Journal | Prenatal diagnosis |
| Volume | 44 |
| Issue number | 2 |
| Early online date | 6 Dec 2023 |
| DOIs | |
| Publication status | Published - Feb 2024 |
Bibliographical note
Copyright © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Funding
The authors thank the Rapid fetal exomes sequencing, Bioinformatics team and the Translational research teams at North Thames Genomic Laboratory Hub. The work described here was partially funded by the NIHR Biomedical Research Centre at the Great Ormond Street Hospital. ASW acknowledges support from the MCR‐NIHR UK Rare Disease Research Platform MR/Y008340/1. ERM acknowledges support from the NIHR Cambridge Biomedical Research Centre (NIHR203312). SS and FM acknowledge the funding provided by the Department for the Economy, Northern Ireland.
| Funders | Funder number |
|---|---|
| MCR‐NIHR UK Rare Disease Research Platform | MR/Y008340/1 |
| Manchester Biomedical Research Centre | |
| Department for the Economy | |
| NIHR Cambridge Biomedical Research Centre | NIHR203312 |
Keywords
- Cohort Studies
- Female
- Humans
- Karyotyping
- Kidney/diagnostic imaging
- Polycystic Kidney Diseases
- Pregnancy
- Prospective Studies