Peter Benn, Yang Wang, Josie Gray, Elizabeth Kramer Dugan, Mark Hajjar, Brittany Prigmore, Vivienne Souter, Barry Wolf
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引用次数: 0
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, 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.
期刊介绍:
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.