RGD Reference Report - Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. - Rat Genome Database

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Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.

Authors: Lind, B  Van Solinge, WW  Schwartz, M  Thorsen, S 
Citation: Lind B, etal., Blood. 1993 Oct 15;82(8):2423-32.
RGD ID: 1578515
Pubmed: (View Article at PubMed) PMID:8400292

Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis. As the nucleotide is a part of the 5 splice site of intron G, it was examined how the mutation affected splicing of protein C pre-mRNA. Relevant protein C cDNA fragments were amplified with polymerase chain reaction after reverse transcription of ectopic mRNA from peripheral blood lymphocytes. Southern blot analysis and nucleotide sequencing of these fragments showed a fragment (A) corresponding to correctly spliced mRNA originating from the normal allele and a fragment (B) corresponding to a truncated mRNA lacking exon 7, originating from the mutant allele. A third fragment (C) lacking exons 7 and 8 was identified in both affected and unaffected family members, as well as in normal controls. Analysis of human liver protein C mRNA indicated that the ectopic lymphocyte mRNA was qualitatively representative for the tissue-specific mRNA. In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency.

Annotation

Disease Annotations    
Venous Thrombosis  (IAGP,ISO)

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