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.
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy. paolo.simioni@unipd.it
Paolo
P
Simioni
Daniela
D
Tormene
Giulio
G
Tognin
Sabrina
S
Gavasso
Cristiana
C
Bulato
Nicholas P
NP
Iacobelli
Jonathan D
JD
Finn
Luca
L
Spiezia
Claudia
C
Radu
Valder R
VR
Arruda
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