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.
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 | 06 Dec 2023 |
| DOIs | |
| Publication status | Early online date - 06 Dec 2023 |
Keywords
- renal genetics
- fetus
- exome sequencing
- Exome/genetics
- Prenatal
Access to Document
- When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis
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