G to C transversion at a splice acceptor site causes exon skipping in the cystatin B gene

Several mutations have been described in the proteinase inhibitor cystatin B gene from individuals affected with progressive myoclonus epilepsy of the Unverricht–Lundborg type (EPM1). One of these mutations, a 1925G→C transition at the 3′-splice acceptor site of the intron 1, was postulated to lead to inappropriate splicing of a primary transcript of the cystatin B gene in EPM1 patients. In an effort to understand the expression of the 1925G→C mutation, the sequence of cystatin B mRNA transcripts from lymphoblastoid cell lines of heterozygous patients carrying the mutation were analyzed. RT-PCR of total mRNA showed two main products: the apparently normal transcript and an aberrant, 102 bp shorter transcript. Direct PCR sequencing showed that the aberrant transcript is a consequence of exon 2 skipping.