A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population.
OBJECTIVE
Factor V (FV) deficiency is a rare bleeding disorder whose molecular bases are poorly characterized. We have recently described a FV missense mutation (Y1702C) predicting reduced FV levels in a thrombophilic patient and in a healthy individual. The aim of the present work was to assess the prevalence of the FV Y1702C mutation among subjects with FV deficiency.


METHODS
Carriership of the FV Y1702C mutation was tested in 8 patients with severe FV deficiency (FV:C <8%), in 16 individuals with asymptomatic partial FV deficiency (mean FV:C 38.0%, SD 11.6%) and in 9 patients with pseudo-homozygous APC-resistance (mean FV:C 46.2%, SD 3.6%). An AccI-restriction protocol was employed for rapid mutation screening.


RESULTS
The FV Y1702C mutation was detected in two unrelated patients with unmeasurable FV levels (one being homozygous and the other doubly heterozygous for a still unknown mutation) and in one subject with partial FV deficiency (FV:C 30%). A striking difference in bleeding phenotype was observed between the homozygous patient and her asymptomatic brother with the same FV genotype. A multi-point FV haplotype analysis was performed in all unrelated carriers of the FV Y1702C mutation. Three haplotypes were found to underlie the mutation in different individuals, suggesting that it might have arisen independently more than once.


CONCLUSIONS
FV Y1702C is a common cause of FV deficiency in the Italian population and might be a recurrent mutation.
Castoldi
E
E
Department of Biochemistry and Molecular Biology, Ferrara University, Italy.
Lunghi
B
B
Mingozzi
F
F
Muleo
G
G
Redaelli
R
R
Mariani
G
G
Bernardi
F
F
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense
D005165:Factor V