M. Giansily-blaizot et al., Analysis of the genotypes and phenotypes of 37 unrelated patients with inherited factor VII deficiency, EUR J HUM G, 9(2), 2001, pp. 105-112
Severe inherited factor VII (FVII) deficiency is a rare autosomal recessive
disorder with a poor relationship between FVII coagulant activity and blee
ding tendency. Both clinical expression and mutational spectrum are highly
variable. We have screened for mutations the FVII gene of 37 unrelated pati
ents with a FVII coagulant activity less than 5% of normal pooled plasmas.
The nine exons with boundaries and the 5' flanking region of the FVII gene
were explored using a combination of denaturing gradient gel electrophoresi
s and direct DNA sequencing. This strategy allowed us to characterise 68 ou
t of the 74 predicted FVII mutated alleles. They corresponded to a large pa
nel of 40 different mutations. Among these, 18 were not already reported. G
enotypes of the severely affected patients comprised, on both alleles, dele
terious mutations which appeared to be related to a total absence of activa
ted FVII. We suggest that this absence of functional FVII can explain the s
evere clinical expression. Whether a small release of FVII is sufficient to
initiate the coagulation cascade and to prevent the expression of a severe
phenotype, requires further investigations.