Summary
To further elucidate the molecular basis for hereditary thrombophilia, we screened
the protein S active gene in 11 families with type I deficiency, using a strategy
based on denaturating gradient gel electrophoresis (DGGE) of all the coding sequences.
Fragments with an abnormal DGGE pattern were sequenced, and 5 novel mutations were
identified in 8 families. The mutations were a 7-nucleotide deletion in exon II, a
4-nucleotide deletion in exon III, a T insertion in exon VII, a C to T transition
transforming Leu 259 into Pro and a T to C transition transforming Cys 625 into Arg
in 4 families. These mutations were the only sequence variations found in the propositus’
gene exons and co-segregated with the plasma phenotype. A total of 28 members of these
8 families were heterozygous for one of the 5 mutations. Twenty-four (58,5%) of the
41 deficient subjects over 18 years of age had clinical thrombophilia, whereas the
13 subjects under 18 were asymptomatic. Of the 28 subjects, 6 (21,5%) were also found
to bear the factor V Arg 506 Gin mutation.
