Test Catalog

Test Id : F13NG

F13A1 and F13B Genes, Next-Generation Sequencing, Varies

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

Detecting the pathogenic alterations within the F13A1 and F13B genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XIII deficiency

 

Genetic confirmation of hereditary factor XIII deficiency with the identification of an alteration in either the F13A1 or F13B gene known or suspected to cause the condition

 

Testing for close family members of an individual with a factor XIII deficiency diagnosis

 

This test is not intended for prenatal diagnosis

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

This test detects pathogenic alterations within the F13A1 and F13B genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XIII deficiency.

 

The gene targets for this test are:

Gene name (transcript): F13A1 (GRCh37 [hg19] NM_000129)

Chromosomal location: 6p24-p25

 

Gene name (transcript): F13B (GRCh37 [hg19] NM_001994)

Chromosomal location: 1q31-q32.1

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

A standard testing algorithm for factor XIII deficiency (FXIIID) has been developed by the Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis (ISTH).(1)

 

Genetic testing for FXIIID is indicated if:

-Factor XIII activity (FXIII) is reduced on a qualitative functional FXIII activity test

-Acquired causes of factor XIII deficiency have been excluded

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

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) Followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing when appropriate

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

F13A1 and B Genes, Full Gene NGS

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

Factor 13 deficiency

FXIIID

F13D

FXIIIA1

FXIIIB

Factor XIII subunit B deficiency

Factor XIII subunit A deficiency

Factor XIIIB deficiency

Factor XIIIA deficiency

Fibrin stabilizing factor deficiency

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

A standard testing algorithm for factor XIII deficiency (FXIIID) has been developed by the Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis (ISTH).(1)

 

Genetic testing for FXIIID is indicated if:

-Factor XIII activity (FXIII) is reduced on a qualitative functional FXIII activity test

-Acquired causes of factor XIII deficiency have been excluded

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Genetic testing should only be considered if reduced factor XIII activity is documented and acquired cases of low factor XIII are excluded.

Shipping Instructions

Ambient and refrigerated specimens must arrive within 7 days of collection, and frozen specimens must arrive within 14 days.

 

Collect and package specimen as close to shipping time as possible.

Necessary Information

Rare Coagulation Disorder Patient Information is required. 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

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD) or light-blue top (3.2% sodium citrate)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability: Ambient (preferred)/Refrigerated/Frozen

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and source of specimen.

2. Provide volume and concentration of the DNA.

Specimen Stability: Frozen (preferred)/Refrigerated/Ambient

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

Forms

1. Rare Coagulation Disorder Patient Information (T824) is required.

2. 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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

3. 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

Blood: 1 mL

Extracted DNA: 100 mcL at 50 ng/mcL concentration

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

Gross hemolysis OK
Gross lipemia OK

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 Ambient (preferred) 7 days
Frozen 14 days
Refrigerated 7 days

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

Detecting the pathogenic alterations within the F13A1 and F13B genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XIII deficiency

 

Genetic confirmation of hereditary factor XIII deficiency with the identification of an alteration in either the F13A1 or F13B gene known or suspected to cause the condition

 

Testing for close family members of an individual with a factor XIII deficiency diagnosis

 

This test is not intended for prenatal diagnosis

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

This test detects pathogenic alterations within the F13A1 and F13B genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XIII deficiency.

 

The gene targets for this test are:

Gene name (transcript): F13A1 (GRCh37 [hg19] NM_000129)

Chromosomal location: 6p24-p25

 

Gene name (transcript): F13B (GRCh37 [hg19] NM_001994)

Chromosomal location: 1q31-q32.1

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

A standard testing algorithm for factor XIII deficiency (FXIIID) has been developed by the Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis (ISTH).(1)

 

Genetic testing for FXIIID is indicated if:

-Factor XIII activity (FXIII) is reduced on a qualitative functional FXIII activity test

-Acquired causes of factor XIII deficiency have been excluded

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Factor FXIII deficiency (FXIIID) is a bleeding diathesis of variable severity. The prevalence of factor FXIII deficiency is currently estimated to be 1 in 2 million but the exact prevalence is unknown. The disorder is inherited in an autosomal recessive manner.

 

Factor XIII is a transglutaminase cross-linking enzyme critical to fibrin clot stabilization. It serves to crosslink alpha and gamma fibrin chains, leading to greater clot strength and resistance to fibrinolysis. Deficiency in FXIII leads to defective crosslinking of fibrin and the formation of a weak, unstable clot. Clots may form properly but break down 24 to 48 hours later, leading to abnormal bleeding. Factor XIII is formed from 2 subunits: catalytic protein FXIII-A, encoded by the F13A1 gene and synthesized by megakaryocytes and certain white blood cells in bone marrow; and stabilizing protein FXIII-B, encoded by the F13B gene and synthesized in the liver. Together, 2 FXIII-A subunits and 2 FXIII-B subunits circulate in plasma as heterotetramer.

 

Patients with FXIII caused by alteration in F13A1 (ie, FXIII-A deficiency) typically have a severe bleeding tendency. Onset of life-threatening symptoms is early and may present as umbilical cord and central nervous system bleeding. Eighty percent to 90% of patients have umbilical bleeding in neonatal period. Forty percent to 60% of patients have spontaneous intracranial haemorrhage within first 2 decades of life, making early diagnosis critical. In women, miscarriage, menorrhagia, and intraperitoneal bleeding are common without prophylaxis. Delayed wound healing is sometimes seen. Subjects with heterozygous alterations may be at risk for bleeding complications following surgery, dental extraction, or trauma. Patients with FXIII caused by alterations in F13B (FXIII-B deficiency) typically have a relatively milder bleeding tendency relative to individuals with FXIII-A deficiency.

 

The unpredictable nature of symptoms in FXIII deficiency, its apparent rarity, and limitations in the development of laboratory tests for its detection, especially when activity levels are very low, have made genotype-phenotype correlation difficult.(2) Additionally, any correlation may be impractical given the high risk of intracranial bleeding among all affected patients and the recommendation of a general prophylactic strategy at the time of diagnosis.(2) However, in general, individuals with virtually undetectable functional activity typically have a severe bleeding tendency. FXIII levels between 1 and 4 IU/dL produce moderate to severe bleeding episodes. It is difficult to predict bleeding pattern in patients with alterations that cause activity level to be greater than 5%.(3) Heterozygotes (ie, individuals with only 1 pathogenic alteration in either F13A1 or F13B) have 50% to 70% factor activity and are typically asymptomatic, although serious bleeding episodes have been reported.(4)

 

Causes of acquired (nongenetic) factor XIII deficiency that should be excluded prior to genetic testing include several medical conditions, such as major surgery, leukemia, liver disease, Henoch-Schonlein purpura (HSP), pulmonary embolism, stroke, inflammatory bowel diseases, sepsis, and disseminated intravascular coagulation. In these acquired FXIII-deficient states, FXIIIA levels drop into the 30% to 70% range. Valproate induces a decrease in FXIII level. FXIII antibodies may develop spontaneously in patients long treated with drugs such as isoniazid, penicillin, phenytoin, practolol, and amiodarone. Development of antibodies are also reported in some cases of severe FXIII deficiency, monoclonal gammopathy of undetermined significance, rheumatoid arthritis, and systemic lupus erythematosus. Factor XIII may also develop spontaneously in older adult patients.

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 provided

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Consultations with the Mayo Clinic Special Coagulation Clinic, Molecular Hematopathology Laboratory, or Thrombophilia Center are available for DNA diagnosis cases. This may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical:

Some individuals may have a variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of factor XIII deficiency. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Technical Limitations:

Next-generation sequencing (NGS) may not detect all types of genetic variants. Additionally, rare variants (ie, polymorphisms) may be present that could lead to false-negative or false-positive results. Therefore, test results should be interpreted in the context of activity and antigen measurements, clinical findings, family history, and other laboratory data. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion and duplication analysis. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If multiple alterations are identified, NGS is not able to distinguish between alterations that are found in the same allele ("in cis") and alterations found on different alleles ("in trans"). This limitation may complicate diagnosis or classification and has implications for inheritance and genetic counseling. To resolve these cases, molecular results must be correlated with clinical history, activity and antigen measurements, and family studies.

 

Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common alterations (ie, polymorphisms) identified for this patient are available upon request.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

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

1. Kohler HP, Ichinose A, Seitz R, et al: Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost. 2011 Jul;9(7):1404-1406

2. Karimi M, Bereczky Z, Cohan N, Muszbek L: Factor XIII deficiency. Semin Thromb Hemost. 2009 Jun;35(4):426-438

3. de Moerloose P, Schved JF, Nugent D: Rare coagulation disorders: fibrinogen, factor VII and factor XIII. Haemophilia. 2016 Jul;22(Suppl 5):61-65

4. Dorgalaleh A, Rashidpanah J: Blood coagulation factor XIII and factor XIII deficiency. Blood Rev. 2016 Nov;30(6):461-475

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

Next-generation sequencing (NGS) and/or Sanger sequencing are performed.

 

Regions of homology, high guanine-cytosine (GC)-rich content, and repetitive sequences may not provide accurate sequence. Therefore, all reported alterations detected by NGS in these regions are confirmed by an independent reference method. However, this does not rule out the possibility of a false-negative result in these regions.

 

Sanger sequencing is used to confirm alterations detected by NGS when appropriate.(Unpublished Mayo method)

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.

Varies

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.

21 to 28 days

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

Whole Blood: 2 weeks; DNA: Indefinitely

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 US 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.

81479

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
F13NG F13A1 and B Genes, Full Gene NGS 92991-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
113076 F13NG Result 50397-9
113070 Alterations Detected 82939-0
113069 Interpretation 69047-9
113071 Additional Information 48767-8
113072 Method 85069-3
113073 Disclaimer 62364-5
113074 Panel Gene List 48018-6
113075 Reviewed By 18771-6

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 | Create a 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