Insights into the Molecular Genetic of Hemophilia A and Hemophilia B: The Relevance of Genetic Testing in Routine Clinical Practice

Abstract

Hemophilia A and hemophilia B are rare congenital, recessive X-linked disorders caused by lack or deficiency of clotting factor VIII (FVIII) or IX (FIX), respectively. The severity of the disease depends on the reduction of coagulation FVIII or FIX activity levels, which is determined by the type of the pathogenic variants in the genes encoding the two factors (F8 and F9, respectively). Molecular genetic analysis is widely applied in inherited bleeding disorders. The outcome of genetic analysis allows genetic counseling of affected families and helps find a link between the genotype and the phenotype. Genetic analysis in hemophilia has tremendously improved in the last decades. Many new techniques and modifications as well as analysis softwares became available, which made the genetic analysis and interpretation of the data faster and more accurate. Advances in genetic variant detection strategies facilitate identification of the causal variants in up to 97% of patients. In this review, we discuss the milestones in genetic analysis of hemophilia and highlight the importance of identification of the causative genetic variants for genetic counseling and particularly for the interpretation of the clinical presentation of hemophilia patients.

Multicenter Study of Diagnostic Tool for Patients with Hemophilia: From Bedside to Comprehensive Investigations

“… 21 , 22 Genetic testing in routine clinical practice is relevant for complete genetic counseling. 23 The definite diagnosis of carriers among family members could be further determined. Alternatively, the informative markers using the linkage analysis of restriction fragment length polymorphisms on the factor VIII and factor IX genes could be provided for regional hospitals to use in both carrier and prenatal diagnosis.…”

A curated census of pathogenic and likely pathogenic UTR variants and evaluation of deep learning models for variant effect prediction

“…This finding aligns with the notion that such related conditions as hemoglobinopathies are among the most prevalent inherited disorders, with genetic mechanisms well studied as a result ( Harteveld et al, 2022 ; Kountouris et al, 2022 ). Pathogenic variant spectra underlying hereditary bleeding disorders including hemophilia and von Willebrand disease have also been studied in detail ( Pezeshkpoor et al, 2022 ), likely contributing to an overrepresentation of implicated genes in our dataset.…”

Exploring Female Relatives of Patients with Hemophilia’ Awareness, Attitudes, and Understanding Towards Genetic Testing [Letter]

“…Genetic testing has increased the number of families with diagnosed defects, while also improving carrier testing and prenatal diagnosis. 3 In their study, Zhao et al tried to gain a better understanding of the knowledge and attitudes of female relatives of PWH towards genetic testing, through qualitative interviewing and/or thematic analysis, which could provide information to support the design and development of genetic counseling services, as well as facilitate the implementation of genetic testing plans for female relatives of PWH. This study is really promising for healthcare systems to manage the diagnosis and treatment of PWH, even though only a small number (11) of female relatives of PWH was included in the study.…”