Evaluating Reproductive Carrier Screening using Biotinidase Deficiency as a Model: Variants Identified, Variant Rates and Management.

Autor:	Benn P; University of Connecticut Health Center, Farmington, CT, USA. Electronic address: benn@uchc.edu., Wang Y; Natera, Inc., Austin, TX, USA., Gray J; Natera, Inc., Austin, TX, USA., Dugan EK; Natera, Inc., Austin, TX, USA., Hajjar M; Natera, Inc., Austin, TX, USA., Prigmore B; Natera, Inc., Austin, TX, USA., Souter V; Natera, Inc., Austin, TX, USA., Wolf B; Division of Genetics, Birth Defects and Metabolism, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Emeritus, Departments of Medical Genetics and Pediatrics, Henry Ford Hospital, Detroit, MI, USA.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Dec 13, pp. 101345. Date of Electronic Publication: 2024 Dec 13.
DOI:	10.1016/j.gim.2024.101345
Abstrakt:	Purpose: To review biotinidase gene (BTD) variants identified in a large, diverse, reproductive carrier screening (RCS) cohort and outline management of heterozygotes with pathogenic or likely pathogenic (P/LP) variants. Methods: This retrospective observational study included samples tested from January 2020 to September 2022 in a 274-gene panel. The study involved females aged 18 to 55 years. Screening was performed using next generation sequencing covering exons and 10 base-pair flanking introns. The heterozygote frequency was calculated for P/LP variants for the entire population and individual racial/ethnic groups. Results: Of the 91,637 women tested, 5,625 (6.1%) had a P/LP variant in BTD. NM_000060.4:c.1330G>C p.(Asp444His) (referred to as D444H or D424H) alone, or in combination with another variant, accounted for 5,193 (92.3%) of the positive tests. P/LP heterozygote rates differed between racial and ethnic groups. We ascertained seven novel P/LP variants not previously recorded in databases. Conclusions: The BTD P/LP variants identified through RCS were substantially compatible with those found through positive newborn screening. Therefore, RCS provides a potential for earlier diagnosis. We observed significant differences in P/LP heterozygote rates for biotinidase deficiency among different racial and ethnic groups. Most reported variants can be interpreted without requiring determination of serum biotinidase activity. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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