Test Catalog

Test ID: F9KMP    
Hemophilia B, F9 Gene Known Mutation Analysis, Prenatal

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

Prenatal testing for a known familial pathogenic mutation in the F9 gene in a fetus who is at risk for inheriting this mutation

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

Hemophilia B is an X-linked disorder caused by mutations in the F9 gene. This test is intended to prenatally detect a previously confirmed familial mutation (missense, nonsense, splice site variants, and small intragenic deletions/insertions) in an at-risk fetus. This mutation should be confirmed and documented in an affected family member and/or confirmed in the mother of the fetus via molecular testing. Documentation of the specific familial mutation must be provided with the specimen in order to perform this test. Testing will be cancelled if this documentation is not submitted. This test is not validated to detect large deletions or duplications that are a cause of approximately 3% of cases of hemophilia B.

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

If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) 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 peripheral 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 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 B 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.

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 issued that will include specimen information, assay information, background information, and conclusions based on the test results (ie, information about the mutation).

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

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.

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

1. Yoshitake S, Schach BG, Foster DC, et al: Complete nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry 1985;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;26(1):265-268

3. Ketterling RP, Bottema CD, Phillips JA 3rd, Sommer SS: Evidence that descendants of three founders constitute about 25% of hemophilia B in the United States. Genomics 1991;10(4):1093-1096

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