A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population

Background and Objectives. Factor V (FV) deficiency is a rare bleeding diso rder whose molecular bases are poorly characterized. We have recently descr ibed a FV missense mutation (Y1702C) predicting reduced FV levels in a thro mbophilic patient and in a healthy individual, The aim of the present work was to assess the prevalence of the RI Y1702C mutation among subjects with RI deficiency. Design and Methods. Carriership of the FV Y1702C mutation was tested in 8 p atients with severe RV deficiency (FV:C < 8%), in 16 individuals with asymp tomatic partial FV deficiency (mean RI:C 38.0%, SD 11.6%) and in 9 patients with pseudo-homozygous APC-resistance (mean FV:C 46.2%, SD 3.6%). An Accl- restriction protocol was employed for rapid mutation screening. Results. The RI Y1702C mutation was detected in two unrelated patients with unmeasurable RV levels (one being homozygous and the other doubly heterozy gous for a still unknown mutation) and in one subject with partial FV defic iency (FV:C 30%), A striking difference in bleeding phenotype was observed between the homozygous patient and her asymptomatic brother with the same R V genotype. A multi-point RV haplotype analysis was performed in all unrela ted carriers of the FV Y1702C mutation. Three haplotypes were found to unde rlie the mutation in different individuals, suggesting that it might have a risen independently more than once. Interpretation and Conclusions. FV Y1702C is a common cause of FV deficienc y in the Italian population and might be a recurrent mutation. (C) 2001, Fe rrata Storti Foundation.