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.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
MATCC Maternal Cell Contamination, B Yes No
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No

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

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

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR)/Fluorescent DNA Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

F9 Gene Known Mutation, AF or CVS

Aliases
Lists additional common names for a test, as an aid in searching

Christmas Disease

F9

Factor IX Deficiency Molecular Diagnosis

Hemophilia B Carrier Testing

Hemophilia B Genetic Testing

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

Specimen Type
Describes the specimen type validated for testing

Varies

Additional Testing Requirements

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.

Shipping Instructions

Advise Express Mail or equivalent if not on courier service

Necessary Information

Hemophilia B Patient Information is required, see Special Instructions. Testing may proceed without the patient information, however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Results will be reported and also telephoned or faxed, if requested.

 

A. For the purposes of maternal cell contamination studies (MCC), submit the following specimen type from the mother in addition to 1 of the 3 accepted fetal specimen types:

 

Specimen Type: Peripheral blood

Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Lavender top (EDTA) or light blue top (sodium citrate)

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

B. For the purposes of prenatal testing of the fetus, submit only 1 of the following specimens:

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 5-10 mL

Collection Instructions:

1. Optimal timing for specimen collection is during 14 to 18 weeks of gestation, but specimens collected at other weeks of gestation are also accepted.

2. Discard the first 2 mL of amniotic fluid. If the culture will be performed in conjunction with chromosome analysis and alpha-fetoprotein, a total of approximately 25 mL to 30 mL will be needed for the combined studies.

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20-30 mg

Collection Instructions:

1. Collect specimen by the transabdominal or transcervical method.

2. Transfer the chorionic villi specimen to a Petri dish containing transport medium (T095).

3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of the villi and remove any blood clots and maternal decidua.

Specimen Stability Information: Refrigerated (preferred) <24 hours/Ambient

 

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks approximately 90% confluent

Collection Instructions: Submit confluent cultured cells from another laboratory

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated

Additional Information:

1. Place the tubes in a Styrofoam container (T329).

2. Fill remaining space with packing material.

3. Unavoidably, about 1% to 2% of mailed-in specimens are not viable.

4. Bloody specimens are undesirable.

5. If the specimen does not grow in culture, you will be notified within 7 days of receipt.

6. There will be no culture charge.

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

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Amniotic fluid: 10 mL

Chorionic Villi: 5 mg

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

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

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 a single region of the F9 gene, followed by fluorescent DNA sequencing analysis utilizing an Applied Biosystems Inc. (ABI) 3730xl DNA Analyzer.(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;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;17[15]:6087-6102)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

28 to 35 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Extracted DNA indefinitely, patient must opt-out.

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81403

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports