Many diseases are known to be caused by mutations in a persons DNA. The polymerase chain reaction (PCR) is a technique used to amplify specific regions of DNA for analysis. Using PCR we can target those specific regions to identify if a mutation is present or not. This allows us to make a diagnosis or prognosis of a disease or disorder.
The Molecular Haematology laboratory offers investigations for haemochromatosis and disorders of thrombophilia. Below is a brief explanation of the tests on offer.
For details regarding sample requirement please see the Test Database. Results are usually available within 14 working days (excluding weekends) of sample receipt.
The Human Genome Variation Society (HGVS) updated nomenclature for the description of sequence variants in 2016. For ease of users traditional nomenclature is currently used within our reports. Please see below for updated HGVS –nomenclature for current assays:
c.845G>A (p.Cys282Tyr) formerly known as C282Y
c.187C>G (p.His63Asp) formerly known as H63D
c.1691G>A (p.Arg506Gln) formerly known as Factor V Leiden
c.*97G>A (p. formerly known as the G20210A Prothrombin Gene mutation
c.665C>T (p.Ala222Val) formerly known as MTHFR
Factor V Leiden (R506Q) - Activated protein C resistance has been attributed to a single point mutation in the gene that codes for the clotting factor protein Factor V, and termed R506Q-Factor V Leiden. This polymorphism involves a single base pair substitution at position 1691 in the factor V gene, resulting in substitution of the arginine (R) at position 506 by glutamine (Q). The mutation results in an increased risk of thrombosis. Exposure to certain environmental risk factors, such as surgery, pregnancy, or oral contraceptives, can further increase the risk for a venous thrombotic event.
Prothrombin Gene (G20210A) - Prothrombin is the precursor to thrombin, which plays a central role in thrombosis, haemostasis and fibrinolysis. A mutation in the prothrombin gene, a single G to A transition at position 20210, causes an increase in prothrombin and is associated with an increased risk of venous thrombo-embolism.
MTHFR (C677T) - MTHFR is a regulatory enzyme in homocysteine metabolism. A C677T mutation in the gene has been identified and homozygosity for the mutation has been implicated in mild hyperhomocysteinaemia. Hyperhomocysteinaemia results in a 2.5 fold increased risk for venous thrombo-embolic events.
C282Y, H63D - Haemochromatosis is an autosomal recessive disorder of iron overload. The disease is characterised by the progressive accumulation of dietary iron, which can lead to clinical complications including cirrhosis, diabetes, cardiomyopathy, arthritis and hepatocellular carcinoma. Several point mutations have been identified, however two are considered to be of more importance in the disease, C282Y and H63D. 80 – 100% of patients with Hereditary Haemochromatosis are homozygous for the C282Y mutation, and individuals showing compound heterozygosity may also be predisposed to iron overload.
DNA retrieved from samples is currently stored for up to 30 years. Any additional request on an archived sample should be made on a Molecular request form for up to this time period. The quality of the DNA will determine if the request is achievable.
The Molecular Haematology Laboratory is staffed Monday to Friday 09:00 to 17:00. Any samples arriving outside of these hours will be refrigerated overnight and dealt with the next working day. For enquiries telephone 0121 424 0704 to speak to a member of Molecular Haematology staff.
to download a request form (pdf). Please complete request form accurately providing as much relevant information as possible. The laboratory will not accept samples/requests with missing or mislabelled PID.
Further information can be obtained from the following external websites: