SEVERE COAGULATION-FACTOR-V DEFICIENCY CAUSED BY A 4-BP DELETION IN THE FACTOR-V GENE

Factor V (FV) deficiency (parahaemophilia) is an autosomal recessive b leeding disorder with an incidence of 1:10(6). We have studied a young girl with very mild bleeding symptoms and undetectable levels of plas ma factor V antigen and activity (<0.3% and <1.6% of normal, respectiv ely), Both parents showed plasma levels of factor V activity of about 50% of normal, Sequence analysis of the 5'- and 3'-untranslated, codin g and adjacent regions of the factor V gene revealed the presence of a 4 bp deletion in exon 13. Subsequent screening of members of the fami ly for the mutation showed that both parents were heterozygous for the mutation, that one healthy sister carried only normal alleles, and th at the patient was homozygous for the mutated allele. The mutation int roduced a frameshift and a novel premature stop codon in codon 1303, a nd would predict the synthesis of a truncated factor V molecule that l acks part of the B domain and the complete light chain, However, no fa ctor V heavy chain could be detected in the plasma of the patient. Fur thermore, factor V activity could not be detected in the patients' pla telets. This is the first reported mutation in the factor V gene that predicts a type I quantitative factor V deficiency, Surprisingly, the patient, who is homozygous for the mutation, so far has only a very mi ld bleeding tendency.