Purpose: To characterize the effect on mRNA splicing of a yet undescribed mutation located in intron 13 splice-donor sequence (IVS13 + 3A --> C) in the Rab-Escort-protein 1 gene of a patient with choroideremia.
Methods: The base substitution was firstly detected by the Single Strand conformation analysis from genomic DNA. A REP-1 cDNA region encompassing exons 10-14 was then specifically amplified from lymphocytes-derived mRNA.
Results: We could demonstrate that this substitution affects REP-1 RNA processing. The patient revealed only one aberrantly spliced mRNA lacking exon 13 and no normal transcript.
Conclusion: The skipping of exon 13 results in the creation of a stop codon at the misspliced junction. This is the first case of nucleotide substitution at the +3 position of a splice donor site so far described in choroideremia.