Hemophilia B, Factor IX Gene Mutation Screening

CPT CODE:

USEFUL FOR:

Ascertaining the causative mutation in the fIX gene of patients withcongenital hemophilia B (factor IX activity deficiency)
Carrier testing of females in whom familial fIX genotype is unknown

SPECIMEN REQUIRED:

Draw blood in a yellow-top (ACD) tube(s), and send 7 mL of ACDwhole blood in original VACUTAINER(S). Invert several times tomix blood. (Green-top [heparin] tube is not acceptable.)Forward unprocessed whole blood promptly at ambienttemperature.Note:    "Hemophilia B Patient Information Sheet" (Supply             T518) is required for all orders. If not ordering                  electronically, please submit information sheet along with                  a "Coagulation Request Form" (Supply T237) with the                  specimen.

TRANSPORT TEMPERATURE:

Ambient\Refrig OK\Frozen OK

CLINICAL INFORMATION:

Hemophilia B, factor IX deficiency, is an X-linked recessivebleeding disorder with an incidence of about 1 per 30,000 live malebirths. This occurs as a result of mutation(s) in factor IX (fIX) gene.As many as 1/3 of hemophiliacs have no affected familymembers, reflecting a high mutation rate (de novo mutations).Hemophilia B affects males, however, all male offspring will benormal, and although all female offspring will be obligatory carriers,they rarely have symptomatic bleeding. In contrast, femaleoffspring of carriers of hemophilia B have a 50% chance of beingcarriers themselves, and each male offspring has a 50% chance ofbeing affected.
Based on factor IX activity, hemophilia B is classified into severe(factor IX activity <1%), moderate (factor IX activity 2%-5%), andmild (factor IX activity 6%-40%) depending on the molecular defect.In males, a low factor IX activity level establishes the diagnosis ofhemophilia B, however, the wide range of normal factor IX activityprecludes an accurate assessment of carrier status in females, thus making molecular testing essential in assessment of carrierstatus.
Inhibitors to factor IX activity are estimated to occur in 5% to 8% ofpatients, much less than that of hemophilia A, and correlates withgenotype typically occurring in patients with deletions of part of allof the fIX gene or in certain nonsense mutations which result in nocirculating factor IX:antigen. More recently, it has been observedthat a subset of patients with such mutations may be at risk ofexperiencing anaphylactic reactions to the factor IX replacementtherapy.
Indirect methods of determining a carrier status by restriction fragmentlength polymorphism (RFLP) are available, however, are limited bythe necessity of a detailed pedigree, DNA specimens from multiplemembers of the family who must be willing to submit a specimen ofblood, and an absolute requirement of an informative polymorphismthat is associated with the defective gene. Even then, accuracy is<100%. The size and X-linked nature of the fIX gene facilitates directmutation analysis which requires DNA from only a limited number offamily members, and the accuracy is close to 100%. The apparentlysmall gain in accuracy of carrier testing has enormous implicationsfor the carriers.

CLINICAL INTERPRETATION:

The interpretive report will contain specimen information, assayinformation, background information, and conclusions based onthe test results (ie, information about the mutation and carrierstatus).

REFERENCE VALUES:

No mutations found 

An interpretive report will be issued which will include specimen

information, assay information, background information, and

conclusions based on the test results (i.e., information about the

mutation and carrier status).