Background: Hereditary Factor VII deficiency is a rare autosomal recessive bleeding disorder. FVII Padua is a variant form that was first described in 1978. It characteristically displays varying levels of FVII activity depending on the origin of the tissue factor used in the thromboplastin assay.

Aims: Here we report a case of a 60-year-old Chinese male presenting incidentally with a prolonged PT identified during a pre-operative consultation; he had no bleeding tendencies.

Methods: Initial evaluation using rabbit brain thromboplastin assay showed 4% FVII activity. Assays using recombinant human tissue factor and human placental thromboplastin showed FVII activity levels of 28% and 21% respectively. FVII antigen levels were at 87%.

Results: Genotype analysis revealed our patient to be a double heterozygote. The Arg364Gln mutation in exon 9 was observed, and this was the mutation originally described in the initial reports of FVII Padua. The other mutation seen was a novel missense mutation in exon 3 (c.260 C>G; Ala87Gly) which corresponds to the gamma-carboxyglutamic (Gla) domain of the protein.

[Prothrombin Results Among Different Assays]

Conclusions: While the clinical significance of the latter mutation is yet to be elucidated, previously reported variants in the Gla domain have been classified as pathogenic. Based on guidelines provided by the American College of Medical Genetics, this mutation can be classified as likely pathogenic. To our knowledge, this is the first report of such a mutation, whether alone or in combination, in patients with FVII deficiency. The use of genotype-phenotype association studies or in silicon analysis may be helpful in predicting the consequences of this mutation.

[Double Heterozygous Mutation in FVII Deficiency]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-double-heterozygous-factor-vii-fvii-deficiency-exon-9-missense-mutation-arg364gln-fvii-padua-and-a-novel-exon-3-missense-mutation-ala87gly/