Choose your country to see the products for your location

P178 F8

SALSA MLPA Probemix P178 F8 detects copy number variations in the F8 gene.

Specifications

Contents: 43 MLPA probes, including 33 probes for F8 covering all 26 exons.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: hemophilia A (HA).

IVDR certified for in vitro diagnostic (IVD) use.

Quick links

List Prices Documentation

Key related products

P011 VWF mix 1

Targets VWF, involved in Von Willebrand disease.

P012 VWF mix 2

Targets VWF, involved in Von Willebrand disease.

P207 F9

Targets F7 and F9, involved in factor VII deficiency and haemophilia B.

P440 F10 + F11

Targets F10 and F11, involved in factor X and factor XI deficiency.

View all

This product has recently been CE-marked for in vitro diagnostic (IVD) use under the In Vitro Diagnostic Regulation (IVDR; EU 2017/746), which replaces the former CE-marking under the IVD Directive (IVDD; Directive 98/79/EC). This update was accompanied by a change in format of the product description. Some information can now be found in a different location (more information).

Intended purpose

The SALSA MLPA Probemix P178 F8 is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative manual assay for the detection of deletions or duplications in the F8 gene in genomic DNA isolated from human peripheral whole blood specimens. P178 F8 is intended to confirm a potential cause for and clinical diagnosis of hemophilia A, and for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Clinical background

Hemophilia A, one of the most common coagulation disorders, is caused by complete or partial deficiency in factor VIII (FVIII) clotting activity. Depending on the remaining level of FVIII clotting activity, three types of hemophilia A can be discriminated: (1) severe hemophilia A with <1% FVIII activity, (2) moderate hemophilia A with 1-5% FVIII activity, and (3) mild hemophilia A with 5-40% FVIII activity (GeneReviews). FVIII functions as a pro-coagulation cofactor and without it, the body is unable to form a stable clot at the site of an injury (Moghadam et al. 2024). Thus, the hallmark of hemophilia is the tendency to bleed (Grigore et al. 2024, Srivastava et al. 2020). Even minor injuries can trigger significant bleeding (Ray et al. 2024).

Hemophilia A is an X-linked recessive disease with a prevalence of approximately 1 in 4,000 live male births that is caused by mutations in the F8 gene encoding FVIII (GeneReviews; Bernardo et al. 2022, Grigore et al. 2024, Letelier et al. 2022, Moghadam et al. 2024). Pathogenic variants causative of hemophilia A span the entire mutation spectrum, i.e. missense mutations, small deletions or insertions, nonsense mutations, splice site mutations, deletions and duplications, and intron inversions (GeneReviews). Specifically, point mutations explain 43-51% of severe hemophilia A cases and 76-99% of moderate or mild hemophilia A cases, and F8 intron 1 and intron 22 inversions account for approximately 2-5% and 43-45% of severe hemophilia A cases, respectively. Presently, F8 intron 1 and intron 22 inversions are not linked to moderate or mild hemophilia A (GeneReviews). Large deletions and duplications account for approximately 5-10% of F8 gene defects causative of disease (https://dbs.eahad.org/FVIII; https://www.cdc.gov/hemophilia/mutation-project/index.html; Guo et al. 2018, Lannoy and Hermans 2022, Li et al. 2023, Pezeshkpoor et al. 2022).

Hemophilia A occurs in females due to different genetic mechanisms. These include heterozygosity for an F8 pathogenic variant associated with skewed inactivation of the normal X-chromosome, homozygosity or compound heterozygosity for two F8 pathogenic variants, or X chromosome abnormalities such as Turner syndrome (Garagiola et al. 2021; Janczar et al. 2020; Shen et al. 2022).

Regulatory status

SALSA MLPA Probemix P178 F8 is CE-marked under the IVDR for in vitro diagnostic (IVD) use in Europe.

This assay is for research use only (RUO) in all other territories.

Product documentation

Version B4

Other versions

Contact us for earlier versions.

Translations and Summary of Safety and Performance

Translations of the product description in selected European languages are available upon request. Please contact us or one of our local sales partners. Translations of the MLPA General Protocol in selected languages are available here.

The Summary of Safety and Performance (SSP) is also available upon request.

List prices

Product

Item no.
Description
Technology
Price
P178-025R
SALSA MLPA Probemix P178 F8 – 25 rxn
MLPA
€ 296.00
P178-050R
SALSA MLPA Probemix P178 F8 – 50 rxn
MLPA
€ 580.00
P178-100R
SALSA MLPA Probemix P178 F8 – 100 rxn
MLPA
€ 1135.00

Required reagents

A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
MLPA MS-MLPA
€ 361.00
EK1-CY5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 361.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1658.00
EK5-CY5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1658.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6373.00

Price details & ordering

The prices above are list prices for direct orders from MRC Holland. Contact us for a quote that takes discounts and additional costs (such as shipping costs) into account. Different prices apply for orders through one of our sales partners; contact your local supplier for a quote.

More information about ordering & prices

Positive samples

Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.

The commercially available positive samples below can be used with the current (B4) version of this product.

  • Coriell NA02325 (f): Heterozygous duplication affecting the probes for F8 exons 1-22.
  • Coriell NA07503 (f): Heterozygous deletion affecting the probes for F8.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P178 F8

  • Azadmehr S et al. (2021). The Spectrum of Pathogenic Variants in Iranian Families with Hemophilia A. Arch Iran Med. 24:887-96.
  • Garagiola I et al. (2021). X Chromosome inactivation: a modifier of factor VIII and IX plasma levels and bleeding phenotype in Haemophilia carriers. Eur J Hum Genet. 29:241-9.
  • Grigore A et al. (2024). Mutational Profile in Romanian Patients with Hemophilia A. Int J Mol Sci. 25:8366.
  • Guo Z et al. (2018). Spectrum of Molecular Defects in 216 Chinese Families With Hemophilia A: Identification of Noninversion Mutation Hot Spots and 42 Novel Mutations. Clin Appl Thromb Hemost. 24:70-8.
  • Johnsen JM et al. (2017). Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative. Blood Adv. 1:824-34.
  • Kim HJ et al. (2012). Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A. Haemophilia. 18:1008-13.
  • Li F et al. (2023). Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants. Front Genet. 14:1254265.
  • Pshenichnikova O et al. (2023). Spectrum of Causative Mutations in Patients with Hemophilia A in Russia. Genes (Basel). 14:260.
  • Shinozawa K et al. (2023). Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation. Res Pract Thromb Haemost. 7:102233.
  • Sun J et al. (2022). F8 gene mutation spectrum in severe hemophilia A with inhibitors: A large cohort data analysis from a single center in China. Res Pract Thromb Haemost. 6:e12723.

References

  • Bernardo Á et al. (2022). Applicability of the Thrombin Generation Test to Evaluate the Hemostatic Status of Hemophilia A Patients in Daily Clinical Practice. J Clin Med. 11:3345.
  • Garagiola I et al. (2021). X Chromosome inactivation: a modifier of factor VIII and IX plasma levels and bleeding phenotype in Haemophilia carriers. Eur J Hum Genet. 29:241-9.
  • Grigore A et al. (2024). Mutational Profile in Romanian Patients with Hemophilia A. Int J Mol Sci. 25:8366.
  • Guo Z et al. (2018). Spectrum of Molecular Defects in 216 Chinese Families With Hemophilia A: Identification of Noninversion Mutation Hot Spots and 42 Novel Mutations. Clin Appl Thromb Hemost. 24:70-8.
  • Janczar S et al. (2020). Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland. Thromb Res. 193:9-14.
  • Lannoy N et al. (2023). Accessibility and visibility of genetic testing for haemophilia across Europe: Where do we stand? Haemophilia. 29:256-73.
  • Letelier A et al. (2022). Silent variant in F8:c.222G>T (p.Thr74Thr) causes a partial exon skipping in a patient with mild hemophilia A. Mol Genet Genomic Med. 10:e1856.
  • Li F et al. (2023). Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants. Front Genet. 14:1254265.
  • Moghadam AA et al. (2024). Relationship between mutations in severe hemophilia A and risk of inhibitor development: A large single-center study. Transfus Apher Sci. 63:104002.
  • Pezeshkpoor B et al. (2022). Insights into the Molecular Genetic of Hemophilia A and Hemophilia B: The Relevance of Genetic Testing in Routine Clinical Practice. Hamostaseologie. 42:390-9.
  • Shen MC et al. (2022). Skewed X-Chromosome Inactivation and Parental Gonadal Mosaicism Are Implicated in X-Linked Recessive Female Hemophilia Patients. Diagnostics (Basel). 12:2267.
  • Srivastava A et al. (2020). WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 26 Suppl 6:1-158.
This site uses cookies to help improve your online experience. Learn more
No, thank you accept

Sign in

Don't have an account? Create one

Forgot password?

Select Your Country

Choose your country to see the products for your location

CE

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

CE2797

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.