Poor relationship between phenotypes of protein S deficiency and mutationsin the protein S alpha gene

By single strand conformational polymorphism, nucleotide sequencing and enz yme restriction, we analyzed the protein S alpha gene in 17 protein S-defic ient probands and in their available family members. The relationship betwe en genotype and phenotype was also evaluated. Twelve different sequence var iations were identified in 17 probands. Ten were putative causal mutations distributed in 16 probands: 4 were nonsense, 5 missense and one a splice si te mutation. In most families in which a mutation was identified, more than one phenotype: of PS deficiency was present. The same splice site mutation (intron j G-A, exon 10+5) was associated with type I deficiency in one fam ily and with type I/III in another unrelated family. A phenotypic discrepan cy was also observed for the Arg474Pro, Gly597Asp and Arg410stop mutations. Glu26Ala, previously reported in kindreds with type I deficiencies, was fo und in association with I, II and LU phenotypes in four unrelated kindreds. Phenotypic analysis of protein S deficiency is poorly related to the under lying genetic defect.