To the Editor:
In their article (Blood 93:1237, 1999) Hunault et al report a patient homozygous for a CG to CG mutation in exon 5 of the factor VII gene, resulting in a Q100R alteration at the amino acid level. They claim that this is the first report of a homozygous patient with this mutation. We would like to draw their attention to the fact that we have described 22 patients from 16 apparently unrelated Norwegian families, of which 17 patients were homozygous for exactly the same mutation. We first reported these patients carrying the Q100R mutation at the XIVth Congress of the International Society on Thrombosis and Haemostasis, New York 1993 (Thromb Haemost 69:612, 1993, abstr. no. 244) and later in a full publication (Thromb Haemost 79:1136, 1998). It is interesting to note the effect of modifying genes. Among our 17 patients, factor VII antigen varied from 10% to 28% of normal controls. The patient described by Hunault was reported to have 12%.
We appreciate this correspondence from Kavlie and Prydz that the identical mutation resulting in factor VII-Gln100Arg was identified in homozygous form in 17 Norwegian patients with factor VII deficiency. As our report was submitted to Blood before publication of their manuscript in Thrombosis and Haemostasisin June 1998, we missed citing their report. The earlier abstract from 1993 did not mention that the patients were homozygous. Their manuscript confirms the hemorrhagic tendency associated with homozygosity for the factor VII-Gln100Arg mutation. The results of the transient expression experiments with the mutant and wild-type cDNAs differ somewhat from ours because they obtained mean levels of factor VII antigen and activity of 57% and 6% of wild type in conditioned media from Chinese hamster ovary cells, respectively, while we obtained levels of 12% and less than 1% in COS-1 cells, respectively. This may be attributable to the use of different cell types and/or assay methods.
The differences in factor VII antigen levels among the Norwegian patients with homozygosity for this mutation are of interest, but it is somewhat surprising to see a substantial difference (28% and 11%), even among 2 young children from one of the families. We agree that there must be modifying genes or environmental influences to explain this difference.