Noninversion Variants in Sporadic Hemophilia A Originate Mostly from Females.
Journal
International journal of molecular sciences
Journal Volume
26
Journal Issue
3
ISSN
1422-0067
Date Issued
2025-01-22
Author(s)
DOI
10.3390/ijms26030891
Abstract
gene inversion variants originate in male germ cells during spermatogenesis. Our recent study revealed that de novo variants (DNVs) caused noninversion variants (NIVs) in sporadic hemophilia A (HA). Here, we conducted a direct clinical determination of sex differences in the origin of sporadic HA-NIV according to the data of two new HA-NIV families, as well as of the families demonstrated in the previous study. Of the 126 registered families with HA, 23 were eligible for inclusion. We conducted a linkage analysis with gene markers and an amplification refractory mutation system-quantitative polymerase chain reaction to confirm the origin of the sporadic NIVs (~0% mutant cells) or the presence of a mosaic variant, requiring further confirmation of the origin in the parent. Two sporadic DNV events were determined. One event occurred in grandparents, consisting of five maternal grandmothers and seven maternal grandfathers, who were the origins; their respective daughters became carrier mothers who gave birth to probands. The other event included 11 mothers, who were the origins exclusively; their respective sons became probands. In this study, we found that sporadic HA-NIVs originate mostly from females (16 out of 23). Our study contributes to a better understanding of the genetic pathogenesis of HA.
Subjects
F8 gene
de novo variant
female
hemophilia A
mosaic variant
noninversion variant
sporadic hemophilia A
SDGs
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Description
Article number 891
Type
journal article