TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: F822B    
Hemophilia A F8 Gene, Intron 22 Inversion Known Mutation, Whole Blood

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

First-tier molecular testing for males affected with severe hemophilia A, when a familial intron 22 inversion has been previously identified

 

Determining hemophilia A carrier status for at-risk females, ie, individuals with a family history of severe hemophilia A due to F8 intron 22 inversion

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 22 inversion within the F8 gene. The intron 22 inversion mutation accounts for approximately 45% of mutations associated with severe hemophilia A.

                                                

Intron 22 inversion known mutation analysis can only be performed for individuals when an intron 22 inversion has already been identified in the family. If a mutation has not already been identified in the family, order F8INV / Hemophilia A F8 Gene, Intron 1 and 22 Inversion Mutation Analysis, Whole Blood.

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

Maternal cell contamination testing will be performed for all cord blood specimens. A maternal whole blood sample with an order for MATCC / Maternal Cell Contamination, Molecular Analysis, Blood is also required to perform this test. (See Specimen Required for more details.)

 

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 5000 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, the most common clinical symptom in individuals with HA, correlates with FVIII activity levels. FVIII activity levels  below 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 22 inversion mutations account for approximately 45% of mutations associated with severe HA. These inversions are typically not identified in patients with mild or moderate HA.

 

Intron 22 inversion known mutation analysis is only recommended for individuals when an intron 22 inversion has already been identified in the family.

 

If a familial mutation has not been identified in a severely affected HA patient the F8 gene intron 1 and 22 inversion analysis (F8INV / Hemophilia A F8 Gene, Intron 1 and 22 Inversion Mutation Analysis, Whole Blood) should be ordered.

 

If the intron 22 inversion analysis is negative, the tested individual has not inherited the familial mutation.

 

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. If the intron inversion assays do not detect an inversion in these individuals, additional analysis (ie, F8 sequencing) may be able to identify the familial mutation. 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.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

The interpretive report will include assay information, background information, and conclusions based on the test results.

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. Consultations with the Mayo Clinic Special Coagulation Clinic, Molecular Hematopathology Laboratory, or Thrombophilia Center are available for DNA diagnosis cases. This may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.

 

Intron 22 inversion known mutation analysis is only recommended for individuals when an intron 22 inversion has already been identified in the family.

This assay detects only F8 intron 22 inversion mutations. Thus, a negative result does not exclude the presence of other mutations in F8.

 

The intron 22 inversion mutation targeted by this assay is found in approximately 45% of individuals with severe hemophilia A; if an intron 22 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. Johnsen JM, Fletcher SN, Huston H, et al: Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv 2017 May;1(13):824-834. doi:10.1182/bloodadvances.2016002923

5. 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