Evaluating reproductive carrier screening using biotinidase deficiency as a model: Variants identified, variant rates, and management
Recommended Citation
Benn P, Wang Y, Gray J, Dugan EK, Hajjar M, Prigmore B, Souter V, and Wolf B. Evaluating Reproductive Carrier Screening using Biotinidase Deficiency as a Model: Variants Identified, Variant Rates and Management. Genet Med 2024; 101345.
Document Type
Article
Publication Date
12-14-2024
Publication Title
Genetics in medicine
Abstract
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, 5625 (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 5193 (92.3%) of the positive tests. P/LP heterozygote rates differed between racial and ethnic groups. We ascertained 7 novel P/LP variants not previously recorded in databases.
CONCLUSION: 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.
PubMed ID
39688110
ePublication
ePub ahead of print
Volume
27
Issue
3
First Page
101345
Last Page
101345
