Abstract
In hemophilia B (HB), factor IX gene (F9) genotyping is used for molecular confirmation of affected individuals, for carrier
testing, to facilitate the identification of those at risk for anaphylaxis/inhibitors
(associated with large deletions), and to assist in assigning disease severity. Owing
to test costs, optimal test utilization involves pre/post-test counseling and appropriate
patient and test selection (e.g., mutation screening [F9MS] vs. known mutation [F9KM] testing). This article aims to review the trends and outcomes of F9-genotyping orders and describe the spectrum of variants identified in a sample of
individuals in our reference laboratory. We performed a retrospective review of consecutive
orders submitted to the Special Coagulation DNA Diagnostic Laboratory, Mayo Clinic,
between 2012 and 2015. A total of 133 orders (38%) were identified for men: 118 (88%)
were F9MS and 15 (12%) were F9KM. Thirteen orders (10%) were cancelled. A total of 209 orders were identified for
women: 178 (85%) were F9MS and 31 (15%) were F9KM. Thirty-seven orders (18%) were cancelled and 30% of the tests performed yielded
negative results. A total of 164 samples (47%) were received without clinical information.
Seventeen previously unreported variants were identified. F9 genotyping provides useful information for HB management; however, 18% of our orders
were cancelled and almost half were received without relevant clinical information,
thus reaffirming the need for ongoing scrutiny of submitted orders. Optimal patient
and test selection is important as is the accurate interpretation of variants identified.
Most of the pathogenic variants identified were point mutations, with very few large
deletions, consistent with the literature.
Keywords
hemophilia B - factor IX - genetic testing
