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DOI: 10.1055/s-0037-1615020
A Novel Mutation in Intron K of the PROS1 Gene Causes Aberrant RNA Splicing and Is a Common Cause of Protein S Deficiency in a UK Thrombophilia Cohort
Supported by a grant from the British Heart Foundation.Publication History
Received
10 October 1997
Accepted after resubmission
04 February 1998
Publication Date:
07 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199806/lookinside/thumbnails/10-1055-s-0037-1615020-1.jpg)
Summary
In the course of investigating the molecular basis of protein S deficiency in 31 index cases with thrombophilia, we identified seven kindred where the underlying defect was a novel A to G transition 9 bp upstream of exon 12 in intron K of the PROS1 gene. In all but one case, the mutation caused type I deficiency. One individual had type III deficiency. While ectopic transcript analysis using the BstXI dimorphism in exon 15 failed to detect a transcript from the mutated allele, analysis of transcripts spanning exons 11 and 12 revealed a minor mRNA species. Sequencing confirmed the mutation created a new RNA acceptor site introducing 8 nucleotides of intronic sequence into the mature mRNA. Haplotype analysis of the defective PROS1 alleles in six families revealed the same haplotype in all affected individuals suggesting the presence of a common ancestor. Six of the fourteen relatives with the mutation experienced at least one venous thrombotic event strongly supporting the association of the mutation with venous thrombosis.
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