Association of deep phenotyping with diagnostic yield of prenatal exome sequencing for fetal brain abnormalities.

Autor:	Drexler KA; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: kathleen.drexler@unchealth.unc.edu., Talati AN; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC., Gilmore KL; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC., Veazey RV; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC., Powell BC; Department of Pediatrics, Division of Genetics and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC., Weck KE; Department of Genetics, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC., Davis EE; Department of Pediatrics, Department of Cell and Developmental Biology, Feinberg School of Medicine, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL., Vora NL; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2023 Oct; Vol. 25 (10), pp. 100915. Date of Electronic Publication: 2023 Jun 13.
DOI:	10.1016/j.gim.2023.100915
Abstrakt:	Purpose: To evaluate whether deep prenatal phenotyping of fetal brain abnormalities (FBAs) increases diagnostic yield of trio-exome sequencing (ES) compared with standard phenotyping. Methods: Retrospective exploratory analysis of a multicenter prenatal ES study. Participants were eligible if an FBA was diagnosed and subsequently found to have a normal microarray. Deep phenotyping was defined as phenotype based on targeted ultrasound plus prenatal/postnatal magnetic resonance imaging, autopsy, and/or known phenotypes of other affected family members. Standard phenotyping was based on targeted ultrasound alone. FBAs were categorized by major brain findings on prenatal ultrasound. Cases with positive ES results were compared with those that have negative results by available phenotyping, as well as diagnosed FBAs. Results: A total of 76 trios with FBAs were identified, of which 25 (33%) cases had positive ES results and 51 (67%) had negative results. Individual modalities of deep phenotyping were not associated with diagnostic ES results. The most common FBAs identified were posterior fossa anomalies and midline defects. Neural tube defects were significantly associated with receipt of a negative ES result (0% vs 22%, P = .01). Conclusion: Deep phenotyping was not associated with increased diagnostic yield of ES for FBA in this small cohort. Neural tube defects were associated with negative ES results. Competing Interests: Conflict of Interest Neeta Vora receives supplies in kind from Illumina for an NIH grant on whole genome sequencing unrelated to the data in this paper. All other authors declare no conflicts of interest. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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