Hemophilia and von Willebrand disease together account for the large majority of congenital
bleeding disorders. Contemporary management, including development of safer clotting
factor concentrates and increased emphasis on long-term follow-up in comprehensive
hemophilia centers, has improved both quality of life and longevity for patients with
congenital bleeding disorders. In addition to facilitating development of recombinant
clotting factor concentrates, isolation and characterization of the respective genes
have led to increasing availability of a repertoire of genetic tests that, although
expensive, are critical for appropriate genetic counseling of affected patients and
their family members. This article provides a practical approach to using genetic
testing for hemophilia A and B.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Mayo Clinic ProceedingsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Biochemistry and physiology of blood coagulation.Thromb Haemost. 1999; 82: 165-174
- Primer on medical genomics, part I: history of genetics and sequencing of the human genome.Mayo Clin Proc. 2002; 77: 773-782
- Primer on medical genomics, part VIII: essentials of medical genetics for the practicing physician.Mayo Clin Proc. 2003; 78: 846-857
- Occurrence of hemophilia in the United States.Am J Hematol. 1998; 59: 288-294
- The molecular basis of hemophilia A in man.Trends Genet. 1988; 4: 233-237
- Definitions in hemophilia: recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis.Thromb Haemost. 2001; 85: 560
- von Willebrand disease masquerading as haemophilia A.Thromb Haemost. 1992; 67: 391-396
- Factor VIII binding assay of von Willebrand factor and the diagnosis of type 2N von Willebrand disease—results of an international survey.Thromb Haemost. 1996; 76: 270-274
- Bleeding Disorders: Investigation and Management. 2nd ed. Blackwell Scientific Publications, Oxford, England1982: 244-245
- Molecular and cellular biology of blood coagulation.N Engl J Med. 1992; 326: 800-806
- Maturation of the hemostatic system during childhood.Blood. 1992; 80: 1998-2005
- Efficacy of self-therapy in hemophilia: a study of 72 patients with hemophilia A and B.N Engl J Med. 1974; 291: 1381-1384
- Use of prophylaxis to prevent complications of hemophilia.Adv Exp Med Biol. 2001; 489: 59-64
- Recombinant clotting factors in the treatment of hemophilia.Thromb Haemost. 1999; 82: 516-524
- A study of liver biopsies and liver disease among hemophiliacs.Blood. 1985; 66: 367-372
- Home-based factor infusion therapy and hospitalization for bleeding complications among males with haemophilia.Haemophilia. 2001; 7: 198-206
- Mortality among males with hemophilia: relations with source of medical care.Blood. 2000; 96: 437-442
- Treatment of haemophilia in the United Kingdom 1981-1996.Haemophilia. 2001; 7: 349-359
- The genetic basis of inhibitor development in haemophilia A.Haemophilia. 1998; 4: 543-545
- Anaphylactic response to factor IX replacement therapy in haemophilia B patients: complete gene deletions confer the highest risk.Haemophilia. 1999; 5: 101-105
- Factor IX inhibitors and anaphylaxis in hemophilia B.J Pediatr Hematol Oncol. 1997; 19: 23-27
- Development of anaphylactic shock in haemophilia B patients with inhibitors.Blood Coagul Fibrinolysis. 1998; 9: S125-S128
- The life cycle of coagulation factor VIII in view of its structure and function.Blood. 1998; 92: 3983-3996
- The molecular basis of hemophilia A: genotype-phenotype relationships and inhibitor development.Semin Thromb Hemost. 2003; 29: 23-30
- Molecular basis of haemophilia A.Haemophilia. 2004; 10: 133-139
- Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.Blood. 1995; 86: 2206-2212
- Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A.Nat Genet. 1993; 5: 236-241
- Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A.Blood. 2002; 99: 168-174
- Factor VIII inhibitors.Thromb Haemost. 1997; 78: 641-646
- Factor IX gene polymorphisms in Indian population.Am J Hematol. 2001; 68: 246-248
- Primer on medical genomics, part II: background principles and methods in molecular genetics.Mayo Clin Proc. 2002; 77: 785-808
- Single-tube polymerase chain reaction for rapid diagnosis of the inversion hotspot of mutation in hemophilia A [letter].Blood. 1998; 92: 1458-1459
- Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.Science. 1985; 230: 1350-1354
- Scanning by DOVAM-S detects all unique sequence changes in blinded analyses: evidence that the scanning conditions are generic.Biotechniques. 2000; 28 (752-753.): 746-750
- Detection of virtually all mutations-SSCP (DOVAM-S): a rapid method for mutation scanning with virtually 100% sensitivity.Biotechniques. 1999; 26 (936-938, 940-942.): 932
- Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.Proc Natl Acad Sci U S A. 1991; 88: 7405-7409
- Detection of three novel mutations in two haemophilia A patients by rapid screening of whole essential region of factor VIII gene.Lancet. 1991; 337: 635-639
- Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII.Cell. 1998; 93: 61-70
- Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.Proc Natl Acad Sci U S A. 1991; 88: 8307-8311
- Assessment of reproductive risks and intentions by mothers of children with hemophilia.Am J Med Genet. 1988; 31: 259-267
- Evidence that descendants of three founders constitute about 25% of hemophilia B in the United States.Genomics. 1991; 10: 1093-1096
- Comparison of direct and indirect methods of carrier detection in an X-linked disease.Am J Med Genet. 1990; 35: 600-608
- Genetic counseling.Am J Hum Genet. 1975; 27: 240-242
- Goals of genetic counseling.Clin Genet. 2001; 60: 323-330
- Primer on medical genomics, part XIII: ethical and regulatory issues.Mayo Clin Proc. 2004; 79: 645-650
- Intrauterine correction of factor VIII (FVIII) deficiency.Haemophilia. 2001; 7: 497-499
- Genetic testing for children and adolescents: who decides?.JAMA. 1994; 272: 875-881
- Intracranial and extracranial hemorrhages in newborns with hemophilia: a review of the literature.J Pediatr Hematol Oncol. 1999; 21: 289-295
- Intracranial haemorrhage as initial presentation of severe haemophilia B: case report and review of Mayo Clinic Comprehensive Hemophilia Center experience.Haemophilia. 2005; 11: 73-77
Article Info
Footnotes
Individual reprints of this article and the entire series on Genetics in Clinical Practice will be available for purchase from our Web site www.mayoclinicproceedings.com.
Identification
Copyright
© 2005 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
