Analysis of a consanguineous pedigree featuring hereditary coagulation factor V deficiency

Objective To screen potential mutation and explore the underlying mechanism for a consanguineous pedigree featuring hereditary coagulation factor V （F V ） deficiency. Methods Clinical diagnosis was validated by coagulant parameter assays of prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （FIB）, FV procoagulant activity （FV ： C） and FV antigen （FV ： Ag）. Potential mutations of the F5 gene in the proband and his family members were analyzed by direct DNA sequencing of PCR products of all exons, exon-intron boundaries and 3r, 51 untranslated regions. Suspected mutation was confirmed by reverse sequencing. Results The PT and APTT in the proband were significantly prolonged, which measured 23.5 s （reference range 11.8-14.8 s） and 50.5 s （reference range 27.0-41.0 s）, respectively. FV activity and FV antigen of the proband were significantly reduced to 8% and ; 1%, respectively. PT and APTT in the younger sister of the proband were also significantly prolonged （24. 1 s and 62. 4 s, respectively）. Her F V activity and F V antigen were also significantly decreased （7% and ; 1;, respectively）. PT and APTT of other family members were within normal range. The homozygous missence mutation causing T→C transition at position 29 170 in exon 5 of F5 gene has resulted in a Phe190Ser substitution in the proband. His younger sister was also homozygous for Phe190Ser. Heterozygosity for Phe190Ser was confirmed in his elder brother, elder sister, two daughters and niece, and their FV activity were slightly decreased （57%,73% ,72% ,66% and 75;, respectively） . A normal wild type was observed in two younger brothers of the proband, and their F V activity and F V antigen were in the normal range. Conclusion Homozygous missence mutation of Phel90Ser has been found in above family featuring hereditary FV deficiency. The homozygous missence mutation was inherited from the parents by consanguineous marriage. Phel90Ser probably underlies may underlie the pathogenesis of hereditary factor V deficiency in this pedigree. Key words: Consanguineous marriage;  Coagulation factor V deficiency;  Gene mutation;  Blood coagulation disorder