Deleterious variants cluster in the A3 domain of factor VIII in people with severe hemophilia A and inhibitors.

ABSTRACT:

Background

Hemophilia A (HA) is an X-linked disorder due to deleterious variants in the factor VIII (FVIII) gene (F8). Few studies from large cohorts have explored F8 genotype in people with HA with origins other than North American and European.

Objectives

We aimed to evaluate the spectrum of F8 variants and haplotypes and affected FVIII domains and chains in the context of inhibitor development in people with severe hemophilia A.

Methods

We performed genotyping of intron 1 and intron 22 inversions (Inv22) and F8 sequencing using a customized gene panel and whole exome sequencing.

Results

We included 265 people with severe hemophilia A. We identified deleterious variants in 98.1% of them, totaling 97 unique mutations, of which 32 (3

SUBMITTER: Zuccherato LW 

PROVIDER: S-EPMC12570200 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature