title: A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate.
abstract: Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for alpha- and beta-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.492_493insT 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 beta-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred.
mesh_terms: D002898:Chromosomes, Human, Pair 8; D003117:Color Vision Defects / Q000235:genetics*; D054815:Cyclic Nucleotide-Gated Cation Channels; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010375:Pedigree; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels