CNGB1 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: beta subunit of the rod cGMP-gated cation channel
  • Involved in the last stage of the phototransduction pathway
  • Closure of the CNGA1/CNGB1 channel in the rod outer segment membrane ultimately leads to hyperpolarisation
Clinical phenotype
(OMIM phenotype no.)
Inheritance
  • Autosomal recessive
Signs for RP
  • Vessels attenuation
  • Waxy optic disc pallor
  • Typical bone spicule pigmentation in the mid-periphery with RPE atrophy
  • Perifoveal RPE atrophy can be observed
  • Posterior subcapsular cataract
Visual function
  • Early-onset disease with slow progressive visual decline
  • Nyctalopia onset during the 1st-2nd decades of life
  • Symptomatic progressive VF loss from a mean age of 33 years (13-40 years old)
  • BCVA usually preserved into adulthood
Systemic features
  • No extraocular features reported
Key investigations
  • ERG: rod-cone dystrophy pattern or non-recordable
  • FAF: central hyper-AF macular ring which progressively shrinks in size over time
  • OCT: Preserved central ellipsoid zone (EZ) within the hyper-AF ring with preserved central subfield thickness; progressive EZ loss over time
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
ManagementOcular
Therapies under research
  • None in clinical trials at present
  • Retinal gene therapy in a mouse model
Further information

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References

  1.  Korschen, H. G., Beyermann, M., Muller, F., Heck, M., Vantler, M., Koch, K.-W., Kellner, R., Wolfrum, U., Bode, C., Hofmann, K. P., Kaupp, U. B. Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors. Nature 400: 761-766, 1999
  2.  Poetsch, A., Molday, L.L., Molday, R.S. The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes. J Biol Chem 276, 48009-48016, 2001
  3.  Winkler, P.A., Ekenstedt, K.J., Occelli, L.M., Frattaroli, A.V., Bartoe, J.T., Venta, P.J., Petersen- Jones, S.M. A large animal model for CNGB1 autosomal recessive retinitis pigmentosa. PLoS One 8, e72229, 2013
  4.  Verbakel SK, van Huet RAC, Boon CJF, et al. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res. 2018;66:157-186
  5.  Bareil, C., Hamel, C. P., Delague, V., Arnaud, B., Demaille, J., Claustres, M. Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum. Genet. 108: 328-334, 2001
  6.  Bocquet, B., Marzouka, N.A., Hebrard, M., Manes, G., Senechal, A., Meunier, I., Hamel, C.P Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations. Mol. Vis. 19, 2487-2500, 2013
  7.  Fradin, M., Colin, E., Hannouche-Bared, D., Audo, I., Sahel, J.A., Biskup, S., Carre, W., Ziegler, A., Wilhelm, C., Guichet, A., Odent, S., Bonneau, D. Run of homozygosity analysis reveals a novel nonsense variant of the CNGB1 gene involved in retinitis pigmentosa 45. Ophthalmic Genet. 37, 357-359, 2016
  8.  Hull, S., Attanasio, M., Arno, G., Carss, K., Robson, A.G., Thompson, D.A., Plagnol, V., Michaelides, M., Holder, G.E., Henderson, R.H., Raymond, F.L., Moore, A.T., Webster, A.R.. Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa. JAMA Ophthalmol., 2017
  9.  Kondo, H., Qin, M., Mizota, A., Kondo, M., Hayashi, H., Hayashi, K., Oshima, K., Tahira, T., Hayashi, K. A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest. Ophthal. Vis. Sci. 45: 4433-4439, 2004
  10.  Michalakis S, Koch S, Sothilingam V, et al. Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Adv Exp Med Biol. 2014;801:733-739

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Updated on November 30, 2020
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