Identify causal F8 gene intron 22A or intron 1 variant in individuals with established severe hemophilia A and determine carrier status of those with relatives with a known inversion of intron 1 or 22A. The most comprehensive test for individuals with severe hemophilia A is Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication (2001614). For mild to moderate hemophilia A, Hemophilia A (F8) Sequencing (2001747) is recommended.
Inverse Polymerase Chain Reaction/Electrophoresis
Within 14 days
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Background Information for Hemophilia A (F8) 2 Inversions:
Characteristics: Severe deficiency of factor VIII clotting activity leading to spontaneous joint or deep muscle bleeding. Moderate to mild deficiency is associated with prolonged bleeding after tooth extractions, surgery, or injuries and recurrent or delayed wound healing.
Incidence: 1 in 4,000-5,000 live male births worldwide, rare in females.
Inheritance: X-linked recessive. Of simplex cases, 85 percent of mothers are carriers and 10-15 percent of boys have a de novo mutation.
Penetrance: 100 percent in males and 10 percent in females.
Cause: Deleterious F8 gene mutations.
Clinical Sensitivity: 51 percent of mutations causing severe hemophilia A are detected by F8 inversion testing. This assay does not detect F8 mutations associated with mild or moderate hemophilia A in males.
Methodology: Intron 22-A and intron 1 inversions detected by inverse PCR and electrophoresis.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. F8 mutations, other than the F8 intron 22-A and intron 1 inversions, will not be detected.
Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2001761||Hemophilia A (F8) Inversions Interp||82343-5|
|2001762||F8 Inv Specimen|
- DNA Analysis for Hemophilia A
- Carrier Detection and Prenatal Diagnosis
- Carrier Detection of Hemophilia A
- F8 Inversion
- Factor VIII Deficiency
- Factor VIII Inversion
- Factor VIII Inversions
- Hemophilia A
- Hemophilia A (Factor VIII) Inversions
- Severe Hemophilia A