Combined Factor V and Factor VIII Deficiency via the MCFD2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4185 MCFD2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4185MCFD281479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Combined Factor V and Factor VIII deficiency (F5F8D) is a disorder highlighted by excessive bleeding. Mild to moderate spontaneous bleeding symptoms including easy bruising, epistaxis, and menorrhagia typically begin in childhood (Zhang 2009). Symptom severity is linked to the amount of Factor V and VIII protein loss with affected individuals having 5-30% of normal levels. In milder cases, bleeding episodes are seen after trauma, child birth, surgery, or dental extractions (Spreafico and Peyvandi 2009). F5F8D is likely underdiagnosed as many patients are asymptomatic until experiencing traumatic events or misdiagnosed as single factor deficiencies. Generally, bleeding episodes are comparable to patients with single deficiencies in Factor V or VIII also making correct diagnosis of F5F8D challenging. Disease occurrence is highest in Middle Eastern Jews and non-Jewish Iranians with an estimated 1 in 100,000 being affected (Neerman-Arbez et al. 1999). Fresh frozen plasma and recombinant Factor VIII have been effective in treated individuals. These treatments are particularly effective as pre-operative therapies to curtail anticipated bleeding episodes (Zhang 2009).

Genetics

F5F8D is inherited in an autosomal recessive manner. Mutations in the LMAN1 or MCFD2 genes are causative for 70% and 30% of cases respectively (Zhang 2006, Zhang 2008). While clinically indistinguishable, individuals with mutations in MCFD2 often have more pronounced decreases in Factor V and VIII protein levels compared to patients with LMAN1 mutations. MCFD2 mutations are found throughout the gene with small insertions or deletions and splicing mutations being most prevalent (Zhang et al. 2003). Missense mutations have also been found at lower frequencies and disrupt MCFD2-LMAN1 interactions. The MCFD2 protein interacts directly with LMAN1 to facilitate intracellular transport of Factor V and Factor VIII proteins between the endoplasmic reticulum and Golgi (Nishio et al 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

MCFD2 mutations have been found in 30% of individuals with F5F8D (Zhang et al. 2006). Analytical sensitivity should be high because all mutations in MCFD2 reported are detectable by this method.

Testing Strategy

This test provides full coverage of all coding exons of the MFCD2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with excess bleeding, prolonged PT and PPT are candidates for testing. Ideal candidates also show decreased FV and FVIII activity indicative of a combined factor deficiency. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MFCD2.

Gene

Official Gene Symbol OMIM ID
MCFD2 607788
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Neerman-Arbez M, Johnson KM, Morris MA, McVey JH, Peyvandi F, Nichols WC, Ginsburg D, Rossier C, Antonarakis SE, Tuddenham EG. 1999. Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency. Blood 93: 2253-2260. PubMed ID: 10090934
  • Nishio M, Kamiya Y, Mizushima T, Wakatsuki S, Sasakawa H, Yamamoto K, Uchiyama S, Noda M, McKay AR, Fukui K, Hauri H-P, Kato K. 2010. Structural basis for the cooperative interplay between the two causative gene products of combined factor V and factor VIII deficiency. Proc. Natl. Acad. Sci. U.S.A. 107: 4034-4039. PubMed ID: 20142513
  • Spreafico M, Peyvandi F. 2009. Combined Factor V and Factor VIII Deficiency. Semin. Thromb. Hemost. 35: 390-399. PubMed ID: 19598067
  • Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, Bosch NB de, Ruiz-Saez A, White GC, Tuddenham EGD, et al. 2003. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat. Genet. 34: 220-225. PubMed ID: 12717434
  • Zhang B, McGee B, Yamaoka JS, Guglielmone H, Downes KA, Minoldo S, Jarchum G, Peyvandi F, Bosch NB de, Ruiz-Saez A, Chatelain B, Olpinski M, et al. 2006. Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2. Blood 107: 1903-1907. PubMed ID: 16304051
  • Zhang B. 2009. Recent developments in the understanding of the combined deficiency of FV and FVIII. Br. J. Haematol. 145: 15-23. PubMed ID: 19183188

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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