We sequenced the human RPE65 gene, which contains fourteen coding exons span-ning 20 kb. Twelve unrelated LCA patients from whom informed consent had been obtained were screened. For each patient, the entire coding and flanking sequences were amplified (Table 1) by PCR from genomic DNA and characterized by singlestrand conformation analysis (SSCA). In one family, an aberrant migration pattern was detected in a product derived from exon 10 (patient III-2 in Fig. 1c). Direct sequencing ofthis exon revealed a deletion of nucleotide A at cDNA position 1067, in a stretch of consecutive adenine residues (Fig. 1a). This mutation, 1067delA, resulted in a frameshift and a premature termina-tion at codon 373, 47 bp downstream from the deletion. This finding prompted us to further sequence the thirteen other RPE65 exons from this patient, who was found to