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A Practical Guide to Laboratory Haemostasis

 

Prothrombin G20210A Mutation



Introduction

The Prothrombin G20210A mutation arises from a single missense mutation [G→A] at position 20210 of the prothrombin gene [F2]. The mutation affects the terminal 3' nucleotide of the 3' untranslated region (UTR) region of the prothrombin mRNA and causes elevated levels of prothrombin in the plasma. Individuals who are heterozygous for the prothrombin G20210A mutation have prothrombin levels that are increased by approximately 30% and homozygous individuals by about 70%. Increased prothrombin levels are associated with increased thrombin generation and correlate with an increased risk of venous thromboembolic disease.

The mutation is a gain-of-function mutation, causing increased cleavage site recognition, increased 3' end mRNA processing leading to an increase in mRNA accumulation and prothrombin synthesis.

Principles & Method

A number of methods exist for the detection of the Prothrombin G20210A mutation. The majority of approaches depend on PCR to amplify genomic DNA followed by a number of methods to identify the presence or absence of the mutation. Such methods include the use of restriction enzymes which cleave the amplified DNA only if the mutation is present, DNA microarrays, real-time PCR, SSCP [Single Strand Conformation Polymorphism Analysis] but there are other approaches.

Interpretation

Most techniques can rapidly distinguish heterozygous individuals from homozygous mutant or wild type [i.e. normal]

Reference Ranges

There are no reference ranges for a genetic test - the mutation is either present in a heterozygous or homozygous form or it is not.

 

Data Interpretation

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