# Mutational Profile in Romanian Patients with Hemophilia A

## TL;DR

This study identifies various genetic mutations in Romanian patients with Hemophilia A, highlighting the genetic diversity and aiding in better clinical management.

## Contribution

The study expands the spectrum of F8 gene variants in Romanian patients and identifies novel mutations.

## Key findings

- 96.3% of patients had pathogenic or likely pathogenic F8 gene variants.
- 21.5% of identified mutations were novel, contributing to genetic diversity.
- Large intron inversion was found in 37.5% of patients.

## Abstract

Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the F8 gene, resulting in deficient or dysfunctional factor VIII (FVIII). This study aimed to characterize the mutational profile of HA in Romanian patients using next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). A total of 107 patients were analyzed, revealing pathogenic or likely pathogenic variants in 96.3% of cases. The identified mutations included missense (30.5%), nonsense (9.1%), small deletions (6.4%), small insertions (2.1%), splice-site variants (4.3%), large deletions (1.6%), and large duplications (1.1%). Large intron inversion was previously found in 37.5% of the patients. Novel variants accounted for 21.5% of identified mutations, expanding the spectrum of F8 variants in this population. This study underscores the genetic heterogeneity of HA and provides insights into genotype–phenotype correlations, aiding in clinical management and prenatal diagnosis.