RGD Reference Report - Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene. - Rat Genome Database

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Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene.

Authors: Romeo, G  Hassan, HJ  Staempfli, S  Roncuzzi, L  Cianetti, L  Leonardi, A  Vicente, V  Mannucci, PM  Bertina, R  Peschle, C 
Citation: Romeo G, etal., Proc Natl Acad Sci U S A. 1987 May;84(9):2829-32.
RGD ID: 1578514
Pubmed: PMID:2437584   (View Abstract at PubMed)
PMCID: PMC304753   (View Article at PubMed Central)

The structure of the gene for protein C, an anticoagulant serine protease, was analyzed in 29 unrelated patients with hereditary thrombophilia and protein C deficiency. Gene deletion(s) or gross rearrangement(s) was not demonstrable by Southern blot hybridization to cDNA probes. However, two unrelated patients showed a variant restriction pattern after Pvu II or BamHI digestion, due to mutations in the last exon: analysis of their pedigrees, including three or seven heterozygotes, respectively, with approximately 50% reduction of both enzymatic and antigen level, showed the abnormal restriction pattern in all heterozygous individuals, but not in normal relatives. Cloning of protein C gene and sequencing of the last exon allowed us to identify a nonsense and a missense mutation, respectively. In the first case, codon 306 (CGA, arginine) is mutated to an inframe stop codon, thus generating a new Pvu II recognition site. In the second case, a missense mutation in the BamHI palindrome (GGATCC----GCATCC) leads to substitution of a key amino acid (a tryptophan to cysteine substitution at position 402), invariantly conserved in eukaryotic serine proteases. These point mutations may explain the protein C-deficiency phenotype of heterozygotes in the two pedigrees.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
thrombophilia  IAGP 1578514DNA:nonsense mutation more ...RGD 
thrombophilia  ISOPROC (Homo sapiens)1578514; 1578514DNA:nonsense mutation more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Proc  (protein C, inactivator of coagulation factors Va and VIIIa)

Genes (Mus musculus)
Proc  (protein C)

Genes (Homo sapiens)
PROC  (protein C, inactivator of coagulation factors Va and VIIIa)


Additional Information