GNAT1 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: G-protein alpha subunit of rod transducin
  • Involved in rod phototransduction
  • Upon light stimulus, the activated protein initiates downstream reactions which eventually leads to photoreceptor hyperpolarisation
Clinical phenotype
(OMIM phenotype no.)
Inheritance
  • Autosomal recessive
  • Autosomal dominant
Ocular features
  • Normal fundus in CSNB
  • Typical RP features +/- perifoveal atrophy
Visual functionCSNB
  • Nyctalopia from early infancy
  • VA and colour vision unaffected
  • Myopia
Autosomal recessive RP
  • Nyctalopia from the 2nd decade of life
  • Progressive VF loss
  • VA variable ranging from 6/6 (80 years old) to 6/24 (32 years old)
Systemic features
  • No extraocular anomalies reported
Key investigationsCSNB
  • ERG: Riggs type with reduced a- and b-wave amplitude under scotopic conditions
RP
  • ERG: absent responses/severe rod-cone dystrophy
  • FAF: Hypo-AF in areas of atrophy
  • OCT: Preserved foveal EZ in one case to marked thinning of the foveal outer retinal layers in another case
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
ManagementOcular
Therapies under research
  • None at present
Further information

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Additional information

GNAT1 missense variants are associated with stationary disease while nonsense variants are associated with progressive retinopathy [8].

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References

  1.  Molday RS, Moritz OL. Photoreceptors at a glance. Journal of Cell Science. 2015 Nov 15;128(22):4039–45
  2.  Dryja TP, Hahn LB, Reboul T, Arnaud B. Missense mutation in the gene encoding the alpha subunit of rod transducin in the Nougaret form of congenital stationary night blindness. Nat Genet. 1996 Jul;13(3):358–60
  3.  Szabo V, Kreienkamp H-J, Rosenberg T, Gal A. p.Gln200Glu, a putative constitutively active mutant of rod α-transducin (GNAT1) in autosomal dominant congenital stationary night blindness. Hum Mutat. 2007 Jul;28(7):741–2
  4.  Naeem MA, Chavali VRM, Ali S, Iqbal M, Riazuddin S, Khan SN, et al. GNAT1 Associated with Autosomal Recessive Congenital Stationary Night Blindness. Invest Ophthalmol Vis Sci. 2012 Mar 13;53(3):1353
  5.  Zeitz C, Méjécase C, Stévenard M, Michiels C, Audo I, Marmor MF. A Novel Heterozygous Missense Mutation in GNAT1 Leads to Autosomal Dominant Riggs Type of Congenital Stationary Night Blindness. Biomed Res Int. 2018;2018:7694801
  6.  Zeitz C, Robson AG, Audo I. Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms. Progress in Retinal and Eye Research. 2015 Mar;45:58–110
  7.  Carrigan M, Duignan E, Humphries P, Palfi A, Kenna PF, Farrar GJ. A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration. Br J Ophthalmol. 2016 Apr;100(4):495–500
  8.  Méjécase C, Laurent-Coriat C, Mayer C, Poch O, Mohand-Saïd S, Prévot C, et al. Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy. Janecke AR, editor. PLoS ONE. 2016 Dec 15;11(12):e0168271

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Updated on November 30, 2020
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