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Ascertaining the causative mutation in the F9 gene of patients with congenital hemophilia B (factor IX activity deficiency)
Carrier testing of females in whom the familial F9 genotype is unknown
Maternal cell contamination testing will be performed for all cord blood specimens. 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
Hemophilia B, factor IX deficiency, is an X-linked recessive bleeding disorder with an incidence of about 1 per 30,000 live male births. It occurs as a result of mutations in the factor IX (F9) gene. As many as one-third of hemophiliacs have no affected family members, which reflects a high mutation rate in the F9 gene (ie, de novo mutations). Hemophilia B affects males. However, all male offspring from an affected male will be normal. Although all female offspring of affected males will be obligatory carriers, they rarely have symptomatic bleeding. In contrast, female offspring of female carriers of hemophilia B have a 50% chance of being carriers themselves and each male offspring has a 50% chance of being affected.
Based on factor IX activity, hemophilia B is classified as severe (factor IX activity <1%), moderate (factor IX activity 1%-5%), or mild (factor IX activity >5%-40%). In males, a low factor IX activity level establishes the diagnosis of hemophilia B. However, the wide range of normal factor IX activity precludes an accurate assessment of carrier status in females, thus making molecular testing essential in assessment of carrier status.
Inhibitors to factor IX activity are estimated to occur in 5% to 8% of hemophilia patients, much less than that of hemophilia A, Inhibitor risk correlates with genotype and typically occurs in patients with either partial or total deletions of the F9 gene or in certain nonsense mutations that result in no circulating factor IX antigen. More recently, it has been observed that a subset of patients with such mutations may be at risk of experiencing anaphylactic reactions to the factor IX replacement therapy.
An interpretive report will be issued which will include specimen information, assay information, background information, and conclusions based on the test results (ie, information about the mutation and carrier status).
Special Coagulation Clinic/Laboratory and Medical Genetics consultations are available for DNA diagnosis cases and may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.
1. Yoshitake S, Schach BG, Foster DC, et al: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry 1985 July 2;24(14):3736-3750
2. Giannelli F, Green PM, Sommer SS, et al: Haemophilia B: database of point mutations and short additions and deletions. Eighth edition. Nucleic Acids Res 1998 Jan 1;26(1):265-268
3. Ketterling RP, Bottema CD, Phillips JA 3rd, et al: Evidence that descendants of three founders constitute about 25% of hemophilia B in the United States. Genomics 1991 Aug;10(4):1093-1096