Abstract

Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for ?- and ?-subunits of the cyclic-nucleotide-gated (CNG) cation channel expressed in cone photoreceptors. High incidence of the disease (1 in 60) was detected in a rural isolate in central Chile. We excluded previously reported mutations in a consanguineous kindred with five affected members. Genotype analysis with short tandem repeat polymorphic (STRP) markers provided evidence to search for the causative mutation in CNGB3. Two sequence variations, c.4923insT and c.488A > G, flanking an adenosine (A 5) repeat in exon 4 were identified. The frameshift mutation creates two consecutive stop codons in exon 5 that would induce premature translation termination. The severely truncated ?-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred.