Acceptor splice site mutation in the invariant AG of intron 5 of the protein C gene, causing type I protein C deficiency.

An acceptor splice-site mutation (3318, A-->G) in the invariant AG of intron 5 of the human protein C gene has been identified in a Spanish family with heterozygous type I protein C (PC) deficiency and thromboembolic disease. Family studies confirmed cosegregation of the mutation with type I PC deficiency. Computer analysis of the mutated sequence predicted the normal splicing site to be abolished by this mutation, whereas a cryptic splice site located two nucleotides downstream, in exon 6, is probably activated. According to this, 3318, A-->G should result in a frameshift with a stop at codon 119, in agreement with the presence of a type I or quantitative PC deficient phenotype in the affected members of the family.