TEST NAME
– Hemophilia A Common Mutation (Factor VIII Intron 22 and Intron 1 Inversion analysis)
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ABOUT 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.
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 on a prenatal specimen can only be performed when there is a known intron 22 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.
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GENES TESTED
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SAMPLE REQUIREMENTS
– EDTA
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TAT
– 17
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Related Tests
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