Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication
Detect causal F8 variant in individuals with established severe hemophilia A and determine carrier status in at-risk females with severely affected male relatives. For mild to moderate hemophilia A, Hemophilia A (F8) sequencing (2001747) is preferred.
Inverse Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
New York DOH Approval Status
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Background Information for Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication:
Characteristics: Severe deficiency of factor VIII clotting activity is associated with spontaneous joint or deep tissue bleeding. Moderate or 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: 98 percent.
Methodology for Inversions: F8 intron 22-A and intron 1 inversions detected by inverse PCR and electrophoresis.
Methodology for Sequencing: Bidirectional sequencing of the F8 coding region and intron-exon boundaries.
Methodology for Deletion/Duplication: Multiplex ligation-dependent probe amplification (MLPA) to detect large deletions/duplications in the F8 coding region.
Analytical Sensitivity & Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region and deep intronic mutations, other than the F8 intron 22-A and intron 1 inversions, will not be detected. Deletions/duplications in exon 23 will not be detected.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
F8 inversion testing is performed on all specimens. If inversion testing does not explain the clinical scenario, then F8 gene sequencing will be added. If inversion testing and sequencing does not explain the clinical scenario, then deletion/duplication testing will be added. Additional charges apply.
81403; if reflexed to Seq, add 81407; if reflexed to Del/Dup, add 81406
|Component Test Code*||Component Chart Name||LOINC|
|2001616||Family History for Hemophilia A (F8)|
|2001617||F8 COMP Specimen|
|2001618||Symptoms for Hemophilia A (F8)|
|2001620||Hemophilia A (F8) Interpretation|
- Carrier Detection and Prenatal Diagnosis
- Carrier Detection of Hemophilia A
- DNA Analysis for Hemophilia A
- Factor VIII
- Factor VIII Deficiency
- Factor VIII Inversion
- Hemophilia A
- Hemophilia A carrier status panel
- Hemophilia A cascade molecular testing
- Hemophilia A reflex panel
- Hemophilia A severe, comprehensive reflex panel
- Severe Hemophilia A