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Test Catalog

Test ID: F10NG    
Factor X Deficiency, F10 Gene, Next-Generation Sequencing, Varies

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

Genetic confirmation of a factor X deficiency diagnosis with the identification of a known or suspected pathogenic alterations in the F10 gene

 

Carrier testing for close family members of an individual with a factor X 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 F10 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor X deficiency (FXD), a rare bleeding disorder.

 

The gene target for this test is:

Gene name (transcript): F10 (GRCh 37 [hg19] NM_000504)

Chromosomal location: 13q34

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

The clinical workup for factor X deficiency (F10D) begins with special coagulation testing for factor X. See F_10 / Coagulation Factor X Activity Assay, Plasma.

 

Genetic testing for F10D is indicated if:

-Factor X clotting activity is reduced (less than 80% of normal)

-Acquired causes of factor X deficiency have been excluded (eg, liver disease, warfarin therapy, vitamin K deficiency, systemic amyloidosis, and inhibitors)

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

Factor X (FX) deficiency (F10D) is a bleeding diathesis of variable severity that may appear at any age, although more severely affected patients, who typically haveFX activity less than 1%, present early in life. Symptoms include umbilical stump bleeding, intracranial hemorrhage, gastrointestinal bleeding, joint bleeds, and hematomas. The most severe clinical symptoms are uncommon in a patient with FX activity levels greater than 2%. Regardless of disease severity, the most common bleeding symptom is nose bleeds. Menorrhagia occurs in more than half of women with F10D but miscarriages are not common. Antepartum and postpartum hemorrhage are reportedly common in women with F10D and also has been reported in heterozygous females.

 

F10D is estimated to affect 1 in 1,000,000 people. If genetic, F10D is inherited in an autosomal recessive manner. Both males and females may be affected.

 

Hereditary F10D results from defects in the concentration or function of coagulation FX, a vitamin-K dependent protein synthesized in the liver that is essential for stopping blood loss after injury. FX circulates in blood plasma as an inactive zymogen. It is activated by either the intrinsic or extrinsic pathway and is the most important activator of prothrombin, which has multiple roles in the hemostatic response to injury.

 

The F10 gene produces coagulation FX. Alterations in the F10 gene can interfere with the production of coagulation FX, leading to lower levels of the factor in blood (type I F10D) or dysfunctional factor protein that is produced in normal amounts (type II F10D). The bleeding tendency in F10D is variable and does not always correlate with circulating FX antigen levels. In general, however, lower FX activity levels predict a higher risk for bleeding. FX activity of less than 1% of normal is associated with severe F10D, activity of 1% to 5% of normal is associated with moderate disease, and a FX activity of 6% to 10% is associated with mild disease. Of note, normal, full-term newborn infants or healthy premature infants may have decreased levels (greater than or equal to 15% to 20% of normal), which may not reach adult levels for greater than or equal to 180 days after birth.

 

Acquired deficiency of FX is more common than hereditary F10D. Causes of acquired (non-genetic) F10D that should be excluded prior to genetic testing include liver disease, warfarin therapy, vitamin K deficiency, and (rarely) inhibitors. Acquired isolated F10D is seen in 6% to 14% of individuals with primary amyloidosis. Other conditions associated with acquired isolated F10D include underlying malignancy, especially acute myeloid leukemia, and respiratory infection. Conditions associated with acquired F10D should be considered prior to genetic testing.

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 mutation that is not identified by the methods performed. The absence of a mutation, therefore, does not eliminate the possibility of factor X deficiency (F10D) or a related disorder. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies (VAF) 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 polymorphisms may be present that could lead to false negative or 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/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 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. Brown DL, Kouides PA: Diagnosis and treatment of inherited factor X deficiency. Haemophilia 2008;14(6):1176-1182

2. Karimi M, Menegatti M, Afrasiable A, et al: Phenotype and genotype report on homozygous and heterozygous patient with congenital factor X deficiency. Haematologica 2008;93(6):934-938

3. Lee G, Duan-Porter W, Metjian AD: Acquired, non-amyloid related factor X deficiency: review of the literature. Haemophilia 2012;18(5):655-663

4. Mumford AD, Ackroyd S, Alikhan R, et al: Guidelines for the diagnosis and management of the rare coagulation disorders: a United Kingdon Haemophilia Centre Doctors’ Organization guidelines on behalf of the British Committee for Standards in Haematology. Br J Haematol 2014;167(3):304-326

5. Nance D, Josephson NC, Paulyson-Nunez K, et al: Factor X deficiency and pregnancy: preconception counseling and therapeutic options. Haemophilia 2012;18(3):e277-285

6. Palla R, Peyvandi F, Shapiro AD: Rare bleeding disorders: diagnosis and treatment. Blood 2015;125(13):2052-2061

7. Menegatti M, Peyvandi F: Factor X deficiency. Semin Thromb Hemost 2009;35(4):407-415

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