Abstract
Combined factor V and VII deficiency is a rare bleeding disorder, with 3 cases reported in the literature. None of these cases were characterized at a molecular level. We now report a 4th case of factor V and VII deficiency, and for the first time characterize the factor V and VII mutations/polymorphisms in the proband and parents.
Case history: The proband is a 5-year-old female who presented with microscopic hematuria and mild mucosal bleeding. She has 47% FV activity and 38% FVII plasma activity. Her father has a history of delayed wound healing and mild mucosal bleeding and her mother has history of mild epistaxis, menorrhagia and gingival bleeding.
Results: The proband was heterozygous for a novel FV mutation, a one base deletion in exon 4 (524delG) introducing a frameshift and resulting in premature truncation of translation 33 amino acids later. In addition, she was heterozygous for 4 previously described factor VII polymorphisms: a 10-bp insertion [CCTATATCCT] at -323 in the 5′ region of the promoter, a G to A substitution in intron 1a (73 g>a), and the R353Q polymorphism in exon 8 of the F7 gene. These 3 polymorphisms have been found to be in strong allelic association in the Italian population, with mild FVII deficiency (Peyvandi et al, 1999). In addition, a R315W mutation was found in exon 8. This mutation has been reported to decrease both FVII coagulant function and factor X activation (Furlan Freguia et al, 2004). The mother was also heterozygous for FV and FVII deficiency, with FV 524 delG and FVII R315W, while as expected the father was heterozygous for the factor VII allele with the 3 associated FVII polymorphisms (Table 1). Thus the proband is heterozygous for FV deficiency and a compound heterozygote for Factor VII deficiency, inheriting FVII mutations from both parents. This is the first molecular characterization of a family with combined factor V and VII deficiency, and also the first family described with 2 different forms of combined FV and FVII deficiency within the same family. These results are consistent with this syndrome being due to chance co-inheritance of FV and FVII mutations rather than a post-translational defect as seen in combined FV and FVIII deficiency.
Table 1 F5 524delG F7 R315W F7 -323 F7 IVS1 73 g>a F7 R353Q Summary of mutations/polymorphisms in a family with combined factor V and factor VII deficiency. X denotes presence of a given mutation/polymorphism in an individual. Proband X X X X X Mother X X Father X X X
Molecular Characterization of a Patient Presumed to Have Prader-Willi Syndrome
