A new Factor X defect (Factor X Padua 3) - A compound heterozygous betweentrue deficiency (Gly(380)-> Arg) and an abnormality (Ser(334)-> Pro)

We report a novel mutation in Factor X (FX) gene which results in a phenoty pe without any bleeding tendency. The proband has been found to be a compou nd heterozygote between a novel FX true deficiency (Gly(380) --> Arg) and a previously reported dysfunctional mutation Ser(334) --> Pro (FX Marsiglia) . Prothrombin time (PT) and partial thromboplastin time (PTT) were moderate ly prolonged and were fully corrected by the addition of normal serum. Her FX activity level varied between 8% and 19% of normal according to the meth od used whereas the FX antigen level was 40% of the normal control value. A ll the exons, and intron/exon junctions of the FX gene were studied using a combined approach of polymerase chain reaction and conformation sensitive gel electrophoresis. A transversion G to A in exon 8 resulting in the repla cement of Gly380 by Arg was found in the proband, in the father and in a pr oband's brother, whereas heterozygous FX Marsiglia was present in the proba nd's mother and her sister. Gly380 is strictly linked to Ser379, a componen t of the catalytic triad. The substitution of Gly for Arg causes the introd uction of a large charged amino acid which could affect the catalytic funct ion of FX leading to secretion problem, accounting for the cross-reactive m aterial (CRM) negative phenotype. (C) 2001 Elsevier Science Ltd. All rights reserved.