X-linked thrombophilia with a mutant factor IX (factor IX Padua).
We report a case of juvenile thrombophilia associated with a substitution of leucine for arginine at position 338 (R338L) in the factor IX gene (factor IX-R338L). The level of the mutant factor IX protein in plasma was normal, but the clotting activity of factor IX from the proband was approximately eight times the normal level. In vitro, recombinant factor IX-R338L had a specific activity that was 5 to 10 times as high as that in the recombinant wild-type factor IX. The R338 substitution causes a gain-of-function mutation, resulting in factor IX that is hyperfunctional.
Simioni
Paolo
P
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy. paolo.simioni@unipd.it
Tormene
Daniela
D
Tognin
Giulio
G
Gavasso
Sabrina
S
Bulato
Cristiana
C
Iacobelli
Nicholas P
NP
Finn
Jonathan D
JD
Spiezia
Luca
L
Radu
Claudia
C
Arruda
Valder R
VR
D004252:DNA Mutational Analysis; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D019851:Thrombophilia / Q000235:genetics*; D055815:Young Adult
C000592235:factor IX-Padua; D005164:Factor IX