title: Lack of sequence variations in the C4b-BP beta-chain in patients with type III protein S deficiency bearing the Ser 460 to Pro mutation: description of two new intragenic isomorphisms in the C4b-BP beta-chain gene (C4BPB).
abstract: Type III protein S (PS) deficiency, characterized by low levels of free PS and normal total PS levels, is often associated with the Ser 460 to Pro substitution. However, some patients bearing this mutation have normal PS levels, suggesting that another gene defect may account for this phenotype. We postulated that this defect was located in the C4b-BP beta-chain gene (C4BPB) and searched for a mutation in the coding regions of this gene in 35 propositi with type III PS deficiency and bearing the Ser 460 to Pro mutation. No mutations explaining the phenotype of type III PS deficiency were identified. We did, however, find two frequent nucleotide changes, one being located in the donor splice site of intron d and the second in the codon corresponding to Asn 137. We used these two polymorphisms to establish C4BPB gene haplotype in five informative type III PS-deficient families and exclude a role of the C4BPB gene in this phenotype of three of them. Finally, increased C4b-BP beta-chain levels were not responsible for the phenotype of type III PS deficiency as the C4BPB haplotype did not correlate with C4b-BP beta-chain levels.
authors.affiliation: INSERM Unité 428, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Morboeuf
authors.forename: M
authors.initials: M
authors.lastname: Aiach
authors.forename: S
authors.initials: S
authors.lastname: Gandrille
mesh_terms: D000328:Adult; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D050716:Complement C4b-Binding Protein; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018455:Protein S Deficiency / Q000235:genetics*
chemical_list: C055609:C4BPA protein, human; C489165:C4BPB protein, human; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens