title: Identification of three novel mutations in hereditary protein S deficiency.
abstract: We report the application of single-stranded conformation polymorphism (SSCP) analysis to the screening of 15 functionally important Protein S (PS) gene (PS alpha) regions (4.243 Kb) in 6 unrelated families with PS deficiencies. Direct sequencing of the fragments with altered migration patterns led to the identification of the corresponding molecular alterations. A missense mutation, G to T transversion at codon Cys598, and two different alterations, leading either to allelic exclusion, or premature termination of the protein translation: a G to A transition at codon Trp465 and a 1 nt (T) insertion at codon 265, were identified. The 1 nt insertion was observed in three apparently unrelated families but with a common geographical origin and the mutated allele was undetectable in platelet mRNAs of affected individuals. Family analysis confirmed, in each case, a perfect cosegregation of the mutation with the PS deficiency. We conclude that these alterations represent the causative mutations.
authors.affiliation: Dep. de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: T C
authors.initials: TC
authors.lastname: Bustorff
authors.forename: I
authors.initials: I
authors.lastname: Freire
authors.forename: T
authors.initials: T
authors.lastname: Gago
authors.forename: F
authors.initials: F
authors.lastname: Crespo
authors.forename: D
authors.initials: D
authors.lastname: David
mesh_terms: D000483:Alleles; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D017293:Protein S; D012333:RNA, Messenger