title: First de novo mutations in the protein C gene of two patients with type I deficiency: a missense mutation and a splice site deletion.
abstract: In a series of 40 patients with symptomatic protein C deficiency, we identified two sporadic cases with novel mutations that probably affect gene expression. The mutations, a 5-bp deletion of the donor splice site of intron f (nucleotides 3455 to 3459) and a mutation of nucleotide 8523 in exon IX leading to the substitution of Ser 270 by Pro, were not found in the protein C gene of the patients' parents. Transmission of the paternal and maternal protein C alleles was apparently normal on the basis of frequent polymorphisms in exons I, VI, and VIII. We also checked the transmission of the chromosomal material by analyzing the beta-globin gene frameworks and three variable number of tandem repeats (VNTRs). By combining the results of intragenic polymorphism, VNTR and beta-globin gene framework analyses, we were able to exclude nonpaternity and confirm the de novo origin of the mutation.
authors.affiliation: INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Gandrille
authors.forename: B
authors.initials: B
authors.lastname: Jude
authors.forename: M
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: J
authors.initials: J
authors.lastname: Emmerich
authors.forename: M
authors.initials: M
authors.lastname: Aiach
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005914:Globins / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D012694:Serine
chemical_list: D011486:Protein C; D012694:Serine; D005914:Globins