Factor V East Texas

Question 1

individual with Factor v east texas have what mutation

Answer 1

an A > Mutation at nt 2440 of the F5 gene

Question 2

This mutation results in what

Answer 2

novel splice donor and acceptor sites within exon 13 of the F5 gene.

Question 3

The mutation resultant fv mRNA is

Answer 3

shortened

Question 4

the shortened mRNA encodes for

Answer 4

an shortened fV protein “fV-short”.

Question 5

describe fV short

Answer 5

the protein is misisng 702 amino acids from the B-domain, the basic region is within this missing region hence fv short is missing the basic region but retains the acidic region.

Question 6

TFPIa binds FV short causing

Answer 6

Increase in plasma TFPIa
-TFPIa binds fV short as it doesn’t have to compete with the FV basic region (higher affinity) , the clearance of TFPIa is prevented after its binding to fV short.

Question 7

Increased plasma TPFIa causes

Answer 7

the individuals with fV East texas to have a bleeding phenotype.

Question 8

what are the hypothesised reasons for the bleeding phenotype

Answer 8

1. plasma TFPIa is elevated to levels that allow it to inhibit TF-fVIIa independently of fXA.
2. as the TFPIa circulates bound to fV short it can quickly inhibits fXa after formation of the prothrombinase complex.

Question 9

FV east texas is classified as an

Answer 9

indirect gain of function mutation

Question 10

What is a similar bleeding disorder caused by the same mechanism as fV east texas.

Answer 10

FV Amsterdam.