Forms

Factor VII Deficiency via the F7 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits
TEST METHODS

Sequencing

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2127 F7$750.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Rare bleeding disorders (RBD) comprise inherited deficiencies of coagulation factors fibrinogen, FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII (Peyvandi et al. 2012). Factor VII deficiency is the most common RBD and accounts for ~30% of cases. In 10% of people with Factor VII deficiency, no mutations in the F7 gene were identified (McVey et al. 2001). Analytical sensitivity for detection of F7 mutations is >95% as gross deletions have only been reported in two cases (Herrmann et al. 2009; Giansily-Blaizot et al. 2007).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 F7$690.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price

1

$690

2

$730

3

$770

4-10

$840

11-30

$1,290

31-100

$1,670

Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Clinical sensitivity for deletion/duplication analysis is less than 5%. In a series of 192 patients with Factor VII or X deficiency, three patients had gross deletions spanning exons 1-9 (Rath et al. 2015).

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Clinical Features

Factor VII deficiency is an excessive bleeding disorder with clinical heterogeneity ranging from life-threatening to asymptomatic. Common symptoms include epistaxis, easy bruising, gum bleeding, hematoma, hemarthrosis, gastrointestinal bleeding and menorrhagia. Severe Factor VII deficiency represents ~15% of cases with bleeding starting early in life with intracranial and gastrointestinal hemorrhaging (Mariani and Bernardi 2009). Asymptomatic patients often do not display signs of the disorder until traumatic events or surgery. Late onset/mild form of Factor VII deficiency represents more than half of the cases for disease. Acquired Factor VII deficiency occurs as a result of liver disease and hypovitaminosis K (Giansily-Blaizot et al. 2004). Factor VII deficiency exhibits a poor genotype-phenotype relationship, therefore genetic testing may be helpful in refining inheritance patterns of the disease (Herrmann et al. 2009). Treatments for Factor VII deficiency include fresh frozen plasma, plasma derived FVII, and recombinant FVII (Lapecorella et al. 2008).

Genetics

Factor VII deficiency is inherited in an autosomal recessive manner through mutations in the F7 gene. Recurrent mutations have been identified in patients with discordant clinical phenotypes suggesting that either environmental or other inherited components modify disease severity. Missense mutations are found in 80% of case of Factor VII deficiency with the majority residing within exon 8 and disrupting the catalytic domain of the protein (Mariani and Bernardi 2009). Splice site, nonsense, small insertion/deletions, and substitution mutations within the promoter region make up the remaining causative variants for disease (Herrmann et al. 2009; Millar et al. 2000; McVey et al. 2001). Gross deletions have been reported in only two cases to date (Herrmann et al. 2009; Giansily-Blaizot et al. 2007). Complete loss of FVII protein is incompatible with life (Rosen et al. 2005). The F7 gene encodes the serine protease FVII, a pro-coagulation factor. Upon vessel injury, FVII binds to tissue factor and initiates the coagulation cascade through activation of secondary coagulation factors including thrombin, FX, FIX, and FXII (Mariani and Bernardi 2009).

Testing Strategy

Our DNA sequencing test involves bidirectional Sanger sequencing of the entire F7 gene plus ~20 bp of flanking non-coding DNA on either side of each exon. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Patients with epistaxis, prolonged INR (greater than 1.5), and prolonged PT are indicative of Factor VII deficiency. Candidates with FVII:C enzymatic assays showing loss of protein activity (typically <2%) are ideal candidates (Mariani and Bernardi 2009).

Gene

Official Gene Symbol OMIM ID
F7 613878
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Factor VII Deficiency AR 227500

CONTACTS

Genetic Counselors
Geneticist
Citations
  • Giansily-Blaizot M, Verdier R, Biron-Adréani C, Schved J-F, Bertrand MA, Borg JY, Cam-Duchez V Le, LeCam-Duchez V, Briquel ME, Chambost H, Pouymayou K, Dutrillaux F, et al. 2004. Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk? Haematologica 89: 704–709. PubMed ID: 15194538
  • Herrmann FH, Wulff K, Auerswald G, Schulman S, Astermark J, Batorova A, Kreuz W, Pollmann H, Ruiz-Saez A, Bosch N De, Salazar-Sanchez L, Greifswald Factor FVII Deficiency Study Group. 2009. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia 15: 267–280. PubMed ID: 18976247
  • Lapecorella M, Mariani G, International Registry on Congenital Factor VII Deficiency. 2008. Factor VII deficiency: defining the clinical picture and optimizing therapeutic options. Haemophilia 14: 1170–1175. PubMed ID: 19141157
  • Mariani G, Bernardi F. 2009. Factor VII Deficiency. Semin. Thromb. Hemost. 35: 400–406. PubMed ID: 19598068
  • McVey JH, Boswell E, Mumford AD, Kemball-Cook G, Tuddenham EG. 2001. Factor VII deficiency and the FVII mutation database. Hum. Mutat. 17: 3–17. PubMed ID: 11139238
  • Millar DS, Kemball-Cook G, McVey JH, Tuddenham EG, Mumford AD, Attock GB, Reverter JC, Lanir N, Parapia LA, Reynaud J, Meili E, Felton A von, et al. 2000. Molecular analysis of the genotype-phenotype relationship in factor VII deficiency. Hum. Genet. 107: 327–342. PubMed ID: 11129332
  • Peyvandi F. et al. 2012. Haemophilia : the Official Journal of the World Federation of Hemophilia. 18 Suppl 4: 148-53. PubMed ID: 22726099
  • Rath M. et al. 2015. Hamostaseologie. 35 Suppl 1: S36-42. PubMed ID: 26540129
  • Rosen ED, Xu H, Liang Z, Martin JA, Suckow M, Castellino FJ. 2005. Generation of genetically-altered mice producing very low levels of coagulation factorVII. Thromb. Haemost. 94: 493–497. PubMed ID: 16268461
Order Kits
TEST METHODS

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (http://www.hgvs.org).  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options


myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
REQUISITION FORM
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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