title: Absence of linkage between type III protein S deficiency and the PROS1 and C4BP genes in families carrying the protein S Heerlen allele.
abstract: To elucidate the molecular basis of hereditary protein S (PS) deficiency and, in particular, type III or free PS deficiency, the allelic distribution and segregation patterns of the PS gene (PROS1) polymorphisms P626A/G and S460P (PS Heerlen) have been analyzed in a group of 45 proposita suffering from type I or type III PS deficiency. No differences between patients and controls were found in the frequency of the P626A/G alleles. By contrast, the frequency of the PS Heerlen allele in the group of patients with type III PS deficiency (9 of 46 chromosomes, P = .196) was significantly higher (P < .001) than in the control group (1 of 300 chromosomes, P = .003). The A allele of P626A/G was always associated with the P allele of S460P. However, this haplotype did not co-segregate with the type III PS-deficient phenotype in 3 of the families. Furthermore, multipoint linkage analysis excluded the whole PROS1 gene in 1 of these families, which is in agreement with the absence of mutations in the PROS1 gene, as determined by sequence analysis. Finally, linkage analysis with 4 microsatellite markers linked to the C4BPB and C4BPA loci also excluded these two genes. From these results we conclude that, at least in some families, the molecular basis of type III PS deficiency is not due to the Mendelian inheritance of a single defect in the PROS1 or in the C4BP genes.
authors.affiliation: Departament de Genètica Molecular, Institut de Recerca Oncològica, Barcelona, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Espinosa-Parrilla
authors.forename: M
authors.initials: M
authors.lastname: Morell
authors.forename: J C
authors.initials: JC
authors.lastname: Souto
authors.forename: M
authors.initials: M
authors.lastname: Borrell
authors.forename: D
authors.initials: D
authors.lastname: Heine-Suñer
authors.forename: I
authors.initials: I
authors.lastname: Tirado
authors.forename: V
authors.initials: V
authors.lastname: Volpini
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: N
authors.initials: N
authors.lastname: Sala
mesh_terms: D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003167:Complement Activation / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016167:Integrin alphaXbeta2; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D018455:Protein S Deficiency / Q000145:classification / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D016167:Integrin alphaXbeta2; D011506:Proteins