Accessibility and visibility of genetic testing for haemophilia across Europe: Where do we stand?

Introduction: Haemophilia is characterized by bleeding complications resulting from clotting factor VIII (FVIII) or IX (FIX) deficiency. Identifying the causal pathogenic genetic variant denotes a vital aspect of haemophilia management.

Aim: This study evaluated the accessibility and performances of genetic testing for haemophilia across Europe.

Genetic mosaicism in haemophilia: A practical review to help evaluate the risk of transmitting the disease.

Approximately 70% of patients with haemophilia exhibit a clear inheritance pattern, while for the remaining 30%, patients are the first to be diagnosed in their family and are considered sporadic cases. In such a setting, the determination of carrier status and the risk estimation of disease transmission to another child are major challenges for genetic counselling. Large studies have suggested that genetic testing reveals 70% of sporadic patients' mothers are carriers.

Inhibitor epidemiology and genetic-related risk factors in people with haemophilia from Côte d'Ivoire.

Introduction: In Sub-Saharan Africa, inhibitor prevalence data in people with haemophilia (PWH) are scarce, as are data on genetic or treatment-related risk factors.

Aims And Methods: We performed a prospective study on PWH from Côte d'Ivoire to collect data into inhibitor prevalence, create a database of haemophilia genotypes, establish correlations between inhibitor presence and genetic variants identified amongst Ivoirian PWHs and evaluate exposure to CFCs.

Results: The study included 54 unrelated participants (43 severe, four moderate, two mild haemophilia A and five severe haemophilia B).

Incidental finding of unreported large duplication in F8 gene during prenatal analysis: Which management for genetic counselling?

Detection of incidental finding and variant of unknown significance (VUS) during prenatal diagnosis has particularly increased with the emergence of genetic tests such chromosomal microarray analysis (CMA). Many factors and clear guidelines need to be applied in the interpretation of the potential clinical consequences of unreported complex copy number variations (deletions/duplications). From a clinical case where an unreported and not completely intragenic duplication in F8 gene has been identified in a 12-week-old fetus without haemophilia A history documented in the family, we will examine and study the difficulties of interpretation and the challenges that the detection of such variant has on genetic counselling.

Review of molecular mechanisms at distal Xq28 leading to balanced or unbalanced genomic rearrangements and their phenotypic impacts on hemophilia.

The distal Xq28 region is very gene-rich, comprising a relatively large number of low-copy repeats (LCRs) predisposing to genomic rearrangements. The best-known rearrangement at this locus is the F8 intron 22 inversion, responsible for up to 45% of severe hemophilia A (HA) cases. An additional inversion of intron 1 of F8 has more recently been described, affecting 2%-5% of patients with severe HA.