Molecular testing in newborn screening: VUS burden among true positives and secondary reproductive limitations via expanded carrier screening panels.

Autor:	Cook S; Masters Program in Human Genetics and Genetic Counseling, Stanford University, Stanford, CA., Dunn E; Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA. Electronic address: erdunn@stanford.edu., Kornish J; Lucile Packard Children's Hospital, Stanford, CA., Calderwood L; Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA; Lucile Packard Children's Hospital, Stanford, CA., Campion M; Masters Program in Human Genetics and Genetic Counseling, Stanford University, Stanford, CA., Cusmano-Ozog KP; Department of Pathology, Stanford University, Stanford, CA., Tise CG; Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Apr; Vol. 26 (4), pp. 101055. Date of Electronic Publication: 2023 Dec 23.
DOI:	10.1016/j.gim.2023.101055
Abstrakt:	Purpose: Expanded carrier screening (ECS) gene panels have several limitations, including variable content, current knowledge of disease-causing variants, and differing reporting policies. This study evaluated if the disease-associated variants identified in affected neonates who screened positive by California newborn screening (NBS) for an inherited metabolic disorder (IMD) by tandem mass spectrometry (MS/MS) would likely be reported by ECS gene panels. Methods: Retrospective review of neonates referred by the California Department of Public Health for a positive NBS by multianalyte MS/MS from January 1, 2020 through June 30, 2021. Results: One hundred thirty-six neonates screened positive for ≥1 NBS MS/MS indication. Nineteen neonates (14%) were ultimately diagnosed with an IMD, all of whom had abnormal biochemical testing. Eighteen of the 19 underwent molecular testing; 10 (56%) neonates had ≥1 variants of uncertain significance, 9 of whom were of non-White ancestry. ECS panels would have been negative for 56% (20/36) of parents with an affected neonate, 85% (17/20) of whom were of non-White ancestry. Conclusion: The number of variants of uncertain significance identified in this cohort highlights the need for more diversified variant databases. Due in part to the lack of diversity in currently sequenced populations, genomic sequencing cannot replace biochemical testing for the diagnosis of an IMD. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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