title: Severe type I protein C deficiency in a compound heterozygote for Y124C and Q132X mutations in exon 6 of the PROC gene.
abstract: We report the genetic abnormalities in the protein C genes of a Spanish child with neonatal purpura fulminans and disseminated intravascular coagulation, associated with undetectable protein C levels. Direct sequencing of the nine protein C gene exons and their splice junctions indicated that the proband is a compound heterozygote with two mutant protein C gene alleles, Y124C and Q132X, that do not express protein C in plasma. The Y124C mutation was inherited from the mother and is due to a novel A to G transition at nucleotide 3416, which results in the substitution of cysteine for tyrosine 124, a highly conserved amino acid in EGF-like domains. The paternal inherited mutation (Q132X) is a C to T transition at nucleotide 3439, which replaces glutamine 132 with a Stop codon signal. This mutation, if expressed, should result in the synthesis of a truncated protein of 131 amino acids. Y124C or Q132X are present in the heterozygous state in the asymptomatic parents and siblings of the proband, all of which have half the normal plasma levels of protein C. Q123X has also been identified in families where type I PC deficiency is inherited as a clinically dominant trait. Therefore, the presence of the same mutation in a family showing a clinically recessive pattern of inheritance indicates that other factors, apart from the type of protein C gene mutation, are responsible for the clinical expression of protein C deficiency.
authors.affiliation: Molecular Genetics Department, IRO, Hospital Duran i Reynals, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Soria
authors.forename: M
authors.initials: M
authors.lastname: Morell
authors.forename: C
authors.initials: C
authors.lastname: Jiménez-Astorga
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: N
authors.initials: N
authors.lastname: Sala
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002648:Child; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency; D011693:Purpura / Q000235:genetics* / Q000378:metabolism; D017421:Sequence Analysis; D013030:Spain
chemical_list: D011486:Protein C