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Carrier detection in the hemophilias.
D P Lillicrap1, B N White, J J Holden
1Department of Pathology, Queen's University, Kingston, Ontario, Canada.
American Journal of Hematology
|November 1, 1987
Summary
Genetic testing advances hemophilia carrier detection, improving accuracy beyond traditional methods. New gene analysis techniques offer reliable carrier information for families with hemophilia A and B.
Area of Science:
- Genetics and Molecular Biology
- Hematology
Background:
- Carrier detection in hemophilias is crucial for genetic counseling and family planning.
- Traditional methods like pedigree analysis and clotting factor assays provide probabilistic results influenced by X-chromosome inactivation and assay variability.
- Advances in genetic technology and understanding of clotting factor genes have renewed interest in accurate carrier diagnosis.
Purpose of the Study:
- To review and highlight the advancements in carrier detection for hemophilia A and B.
- To emphasize the shift from traditional diagnostic methods to molecular genetic analysis.
- To assess the diagnostic capabilities of new genetic markers for carrier identification.
Main Methods:
- Utilizing gene analysis, specifically Restriction Fragment Length Polymorphisms (RFLPs), as linked markers for defective clotting factor genes (Factor IX and Factor VIII).
- Employing a combination of intragenic and extragenic polymorphic markers for hemophilia A.
- Integrating intragenic RFLPs and protein polymorphism immunoassays for hemophilia B.
Main Results:
- In hemophilia A, the combined use of three intragenic and two extragenic markers enables carrier information for approximately 90% of families.
- In hemophilia B, despite heterogeneous gene expression, the integration of five intragenic RFLPs, one linked RFLP, and two immunoassays allows for accurate carrier assignment in over 80% of families.
- Gene analysis offers a more definitive approach compared to probabilistic outcomes from clotting factor assays.
Conclusions:
- Molecular genetic analysis, particularly RFLP-based methods, significantly enhances the accuracy and accessibility of carrier detection in hemophilia A and B.
- These advanced genetic tools provide more reliable carrier information, aiding in prenatal diagnosis and family management.
- The development of novel genetic markers has overcome limitations of traditional diagnostic approaches in hemophilia.