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CC BY-NC-ND 4.0 · Hamostaseologie 2022; 42(06): 390-399
DOI: 10.1055/a-1945-9429
Review Article

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

Behnaz Pezeshkpoor
1   Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany
2   Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany
,
Johannes Oldenburg
1   Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany
2   Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany
,
Anna Pavlova
1   Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany
2   Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany
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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.

Zusammenfassung

Hämophilie A und B sind seltene angeborene, rezessive X-chromosomale Erkrankungen, die durch einen Mangel an Gerinnungsfaktor VIII (FVIII) bzw. IX (FIX) verursacht werden. Der Schweregrad der Erkrankung hängt von der Verringerung der Gerinnungsaktivitäten von FVIII bzw. FIX ab, die durch die Art der pathogenen Varianten in den Genen für die beiden Faktoren (F8 bzw. F9) bestimmt wird. Die molekulargenetische Analyze wird häufig bei vererbten Blutungsstörungen eingesetzt. Die Ergebnisse ermöglichen eine genetische Beratung der betroffenen Familien und helfen dabei, eine Verbindung zwischen dem Genotyp und dem Phänotyp zu erstellen. Die genetische Analyze der Hämophilie hat sich in den letzten Jahrzehnten enorm verbessert. Viele neue Techniken und Modifikationen sowie Analysesoftware sind inzwischen verfügbar, so dass die genetische Analyze und die Interpretation der Daten schneller und genauer erfolgen kann. Fortschritte bei den Strategien zur Erkennung von genetische Varianten erleichtern die Identifizierung der ursächlichen Varianten bei bis zu 97% der Patienten. In dieser Übersicht werden die Meilensteine der genetischen Analyze der Hämophilie erörtert und die Bedeutung der Identifizierung ursächlicher genetischer Varianten für die genetische Beratung und insbesondere für die Interpretation des Krankheitsbildes von Hämophiliepatienten hervorgehoben.

Keywords

genetic analysis - hemophilia - carriers - next-generation sequencing

Schlüsselwörter

genetische Untersuchung - Hämophilie - Konduktorinnen - “next-generation” Sequenzierung


Publication History

Received: 01 September 2022

Accepted: 08 September 2022

Article published online:
22 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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