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 thromboe mbolic 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, w hereas a cryptic splice site located two nucleotides downstream, in ex on 6, is probably activated. According to this, 3318, A-->G should res ult in a frameshift with a stop at codon 119, in agreement with the pr esence of a type I or quantitative PC deficient phenotype in the affec ted members of the family.