Test ID: FIXKM
Hemophilia B, Factor IX Gene Known Mutation Screening
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Carrier testing of females in whom familial fIX genotype is known
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutation must be provided with the specimen in order to perform this test.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, factor IX known mutation will always be performed at an additional charge.
The following algorithms are available in Special Instructions:
-Hemophilia Carrier Testing Algorithm
-Hemophilia Testing Algorithm
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR)/Fluorescent DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Factor IX deficiency molecular diagnosis
Hemophilia B carrier testing
Hemophilia B genetic testing
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Yellow top (ACD solution B)
Acceptable: EDTA or sodium citrate
Specimen Volume: 6 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Forms: Hemophilia B Patient Information Sheet (Supply T518) in Special Instructions
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | NA |
| Other | Green-top (heparin) tube or cord blood |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
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. This occurs as a result of mutation(s) in factor IX (fIX) gene. As many as 1/3 of hemophiliacs have no affected family members, reflecting a high mutation rate (de novo mutations). Hemophilia B affects males, however, all male offspring will be normal and although all female offspring will be obligatory carriers, they rarely have symptomatic bleeding. In contrast, female offspring of 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 into severe (factor IX activity <1%), moderate (factor IX activity 2%-5%), and mild (factor IX activity 6%-40%) depending on the molecular defect. In males, 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 patients, much less than that of hemophilia A, and correlates with genotype typically occurring in patients with deletions of part of all of the fIX gene or in certain nonsense mutations which 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.
Indirect methods of determining a carrier status by restriction fragment length polymorphism (RFLP) are available, however, are limited by the necessity of a detailed pedigree, DNA specimens from multiple members of the family who must be willing to submit a specimen of blood, and an absolute requirement of an informative polymorphism that is associated with the defective gene. Even then, accuracy is <100%. The size and X-linked nature of the fIX gene facilitates direct mutation analysis which requires DNA from only a limited number of family members, and the accuracy is close to 100%. The apparently small gain in accuracy of carrier testing has enormous implications for the carriers.
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 which will include specimen information, assay information, background information, and conclusions based on the test results (ie, information about the mutation and carrier status).
Interpretation Provides information to assist in interpretation of the test results
The interpretive report will contain specimen information, assay information, background information, and conclusions based on the test results (ie, information about the mutation and carrier status).
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/or 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 Provides recommendations for further in-depth reading of a clinical nature
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-8th 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
Method Description Describes how the test is performed and provides a method-specific reference
Direct mutation analysis of leukocyte genomic DNA performed by PCR amplification of fIX gene, followed by fluorescent DNA sequencing analysis utilizing Applied Biosystem Inc. (ABI):single region. (Costa JM, Ernault P, Vidaud D, et al: Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B. Thromb Haemost 2000 Feb;83[2]:244-247; Kaiser RJ, MacKellar SL, Vinayak RS, et al: Specific-primer-directed DNA sequencing using automated fluorescence detection. Nucleic Acids Res 1989 Aug 11;17[15]:6087-6102)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81403-Known familial variant not otherwise specified, for gene listed in Tier 1 or Tier 2, DNA sequence analysis, each variant exon
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 23763 | F IX Know Mut Reason for Referral | 42349-1 |
| 23764 | Factor IX Known Mutation Method | In Process |
| 23765 | Factor IX Known Mutation Result | 69483-6 |
| 23766 | Factor IX Known Mutation Interp | 69049-5 |
| 23768 | Factor IX Known Mut Reviewed By | In Process |
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