Test Catalog

Test ID: F81P    
Hemophilia A F8 Gene, Intron 1 Inversion Known Mutation Analysis, Prenatal, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Prenatal testing for hemophilia A when a F8 intron 1 inversion has been identified in a family member.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Detects the intron 1 inversion in the F8 gene. The intron 1 inversion mutation accounts for approximately 5% of mutations associated with severe hemophilia A.


Intron 1 inversion known mutation analysis on a prenatal specimen can only be performed when there is a known intron 1 inversion in the family.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If amniotic fluid is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added. A maternal whole blood sample is required to perform this test.


The following algorithms are available in Special Instructions:

-Hemophilia Carrier Testing Algorithm

-Hemophilia Testing Algorithm

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hemophilia A (HA) is caused by a deficiency of clotting factor VIII (FVIII). HA is an X-linked recessive bleeding disorder that affects approximately 1 in 5,000 males. Males are typically affected with bleeding symptoms, whereas carrier females generally do not have bleeding symptoms but are at risk of having affected sons. Rarely, approximately 10% of carrier females have FVIII activity levels below 35% and are at risk for bleeding.


Bleeding is the most common clinical symptom in individuals with HA and correlates with FVIII activity levels. FVIII activity levels of <1% are associated with severe disease, 1% to 5% activity with moderate disease, and 5% to 40% with mild disease. In males with severe deficiency, spontaneous bleeding may occur. In individuals with mild HA, bleeding may occur only after surgery or trauma.


FVIII is encoded by the factor VIII (F8) gene. Approximately 98% of patients with a diagnosis of HA are found to have a mutation in F8 (ie, intron 1 and 22 inversions, point mutations, insertions, and deletions). The intron 1 inversion mutation accounts for approximately 5% of mutations associated with severe HA. This inversion is typically not identified in patients with mild or moderate HA.


Intron 1 inversion known mutation analysis on a prenatal specimen can only be performed when there is a known intron 1 inversion in the family.


It is recommended that the F8 mutation be confirmed in the affected male or obligate carrier female prior to testing at-risk individuals. Affected males are identified by FVIII activity (F8A / Coagulation Factor VIII Activity Assay, Plasma) and clinical evaluation, while obligate carrier females are identified by family history assessment. Of note, not all females with an affected son are germline carriers of a F8 mutation, as de novo mutations in F8 do occur. Approximately 20% of mothers of isolated cases do not have an identifiable germline F8 mutation. Importantly, there is a small risk for recurrence even when the familial F8 mutation is not identified in the mother of the affected patient due to the possibility of germline mosaicism.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Not applicable

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Obtaining a medical genetics or hematology (coagulation) consultation prior to ordering is advisable. Molecular genetic or hemophilia center consultation is available for all possible hemophilia A cases and is particularly indicated in complex cases or in situations in which the diagnosis is atypical or uncertain.


This assay detects only the F8 intron 1 inversion mutation. Thus, a negative result does not exclude the presence of other mutations in F8.


The intron 1 inversion mutation targeted by this assay is found in approximately 5% of individuals with severe hemophilia A; if an intron 1 inversion has not been already identified in the family, the assay may be uninformative.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions in severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212

2. Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039

3. Castaldo G, D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med 2007;45(4):450-461

4. Pruthi RK: Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc 2005;80:1485-1499

Special Instructions Library of PDFs including pertinent information and forms related to the test