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.

• Authors: Cecilia V Rojas, Lorena Santa María, José Luis Santos, Fanny Cortés, María Angélica Alliende
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 10 Issue 10 Pg. 638-42 (Oct 2002) ISSN: 1018-4813 [Print] England
• PMID: 12357335 (Publication Type: Journal Article)

Chemical References

• Cyclic Nucleotide-Gated Cation Channels
• Ion Channels

Topics

• Chromosomes, Human, Pair 8
• Color Vision Defects (genetics)
• Cyclic Nucleotide-Gated Cation Channels
• Female
• Frameshift Mutation
• Humans
• Ion Channels (genetics, metabolism)
• Male
• Pedigree
• Retinal Cone Photoreceptor Cells (metabolism)