FACTOR-VII TOYAMA (THR-359-MET) - A HOMOZYGOUS MISSENSE MUTATION CAUSING SEVERE TYPE-I DEFICIENCY

We performed a DNA analysis on a patient with severe type I factor VII deficiency by the polymerase chain reaction amplification and a direc t DNA sequencing method. The proband was a 66-year-old Japanese woman who had recurrent episodes of excessive bleeding after dental extracti on. The functional and antigenic levels of plasma factor VII markedly reduced to 1.6% and 2% of normal, respectively. However. she had no se rious symptoms such as intracranial or intraarticular hemorrhage. The analysis revealed that the patient was homozygous for a missense mutat ion, Thr (A (C) under bar G) to Met (A (T) under bar G) at codon 359 i n the catalytic domain. Her deceased parents were first cousins, and t heir consanguineous marriage presumably resulted in the homozygosity i n her. This patient was the first case of homozygote for the Thr359Met mutation, though heterozygotes for the mutation were previously found in an Italian family.