CNGA1 gene

Overview

Gene (OMIM No.)	CNGA1 (#123825)
Function of gene/protein	Protein: alpha subunit of the rod cGMP-gated cation channel Involved in the last stage of the phototransduction pathway Closure of the CNGA1/CNAGB1 channel in the rod outer segment membrane ultimately leads to hyperpolarisation
Clinical phenotype (OMIM phenotype no.)	Autosomal recessive retinitis pigmentosa: Retinitis pigmentosa 49 (#613756)
Inheritance	Autosomal recessive
Signs for RP	Vessels attenuation Waxy optic disc pallor Bone spicule pigmentation in the mid-periphery (sparse) Retinal degeneration involving the macular in advanced stages
Visual function	Autosomal recessive CNGA1 retinopathy Early-onset nyctalopia, usually in the 1st decade VF loss usually during the 3rd decade of life but can be as early as the 1st decade Gradual decline of BCVA from the 4th decade
Systemic features	No extraocular features reported
Key investigations	ERG: rod-cone dystrophy pattern or non-recordable FAF: Central hyper-AF macular ring OCT: Preserved outer retinal layers within the hyper-AF ring while there is outer retinal loss and beyond the ring
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Ocular Management of RP
Therapies under research	None at present
Further information	OMIM

Dhallan, R. S., Macke, J. P., Eddy, R. L., Shows, T. B., Reed, R. R., Yau, K.-W., Nathans, J. Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression. J. Neurosci. 12: 3248-3256, 1992
Dryja, T. P., Finn, J. T., Peng, Y.-W., McGee, T. L., Berson, E. L., Yau, K.-W. Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc. Nat. Acad. Sci. 92: 10177-10181, 1995
Zhong, H., Molday, L. L., Molday, R. S., Yau, K.-W. The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420: 193-198, 2002
Katagiri S, Akahori M, Sergeev Y et al. Whole Exome Analysis Identifies Frequent CNGA1 Mutations in Japanese Population with Autosomal Recessive Retinitis Pigmentosa. PLoS ONE. 2014;9(9):e108721
Jin X, Qu LH, Hou BK, et al. Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family. Biosci Rep. 2016;36(1):e00289
Gao Q, Liu Y, Lei X, et al. A Novel CNGA1 Gene Mutation (c.G622A) of Autosomal Recessive Retinitis Pigmentosa Leads to the CNGA1 Protein Reduction on Membrane. Biochem Genet. 2019;57(4):540-554
Zhang Q, Zulfiqar F, Riazuddin SA, et al. Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation. Mol Vis. 2004;10:884-889

Updated on November 30, 2020