SCIENTIFIC BACKGROUND

F8

Category:

SCIENTIFIC BACKGROUND

Hemophilia A is an X-linked recessive coagulation disorder caused by a deficiency of coagulation factor VIII (FVIII). This leads to a disturbance in the intrinsic pathway of the coagulation cascade and hemorrhagic diathesis with prolonged activated partial thromboplastin time (aPTT).

 

Phenotypically, hemophilia A is indistinguishable from hemophilia B (factor IX deficiency). The two syndromes can be differentiated by biochemical measurement of the respective enzyme activity. Factor XIII activity should be measured before genetic testing. Since von Willebrand factor deficiency can also lead to decreased FVIII activity, von Willebrand factor should also be determined biochemically for a differential diagnosis.

 

More than 2,500 pathogenic variants in the F8 gene are known to lead to hemophilia A. Depending on the type of variant, there is a varying degree of impairment of enzyme activity; as a result the disease is classified into different levels of severity:

  • Severe hemophilia A: factor VIII activity <1%
  • Moderate hemophilia A: factor VIII activity 1-5%
  • Mild hemophilia A: factor VIII activity 6-40%

 

Due to X-linked inheritance, males are predominantly affected. The estimated prevalence is approximately 1:6,000. In rare cases, heterozygous carriers may also express symptoms in the presence of unequal X inactivation. Approximately 30% of hemophilia A cases are due to new mutations. Mild forms and about 50% of severe forms of the disease are caused by point mutations in the F8 gene. About half of the severe hemophilia cases are caused by gene inversions in intron 1 or intron 22. Therapy involves intravenous substitution with recombinant factor VIII.

 

References

Konkle et al. 2000 Oct 2 [Updated 2017 Jun 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. Gene Reviews®, [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK1495 / Jenkins et al. 2012, Eur J Hum Genet 20:5 / Oldenburg et al. 2008, Hämostaseologie 28:335 / Keeney et al. 2005, Haemophilia 11:87 / http://www.dhg.de/

GENES

F8

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more