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The GNAT1 gene codes for transducin which stimulates the coupling of rhodopsin and cGMP-phosphodiesterase in rods and cones.
The GNAT1 gene codes for transducin which stimulates the coupling of rhodopsin and cGMP-phosphodiesterase in rods and cones.

Night Blindness, Congenital Stationary, CSNBAD3

Clinical Characteristics

Ocular Features

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 9 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable.

This disorder (CSNBAD3), one of three autosomal dominant CSNB conditions, is known primarily from  a single large family in Southern France.  All affected individuals descended from Jean Nougaret from which the eponym is derived.  The published pedigree by F. Cunier in 1838 is probably the first illustrating autosomal dominant inheritance of a human disease.  Rod a-waves are completely absent suggesting complete lack of rod function.  Night vision in dim conditions was reduced but not with bright backgrounds.  Daytime vision is normal as is color vision.  Rare patients have peripheral pigmentary changes with visual field restriction.

Systemic Features

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNBAD3, or type AD3, is one of three congenital nightblindness disorders with autosomal dominant inheritance.  It results from mutations in the GNAT1 gene (3p21) gene encoding a subunit of rod transducin which couples rhodopsin as part of the phototransduction cascade.

A consanguineous Pakistani family with 4 affected children in a pedigree suggestive of autosomal recessive inheritance has been reported.  All individuals with congenital nightblindness were homozygous for a missense mutation in GNAT1 while unaffected persons were heterozygous.

Other autosomal dominant CSNB disorders are: CSNBAD2 (163500) and CSNBAD1 (610445).  Three CSNB disorders are transmitted in an autosomal recessive pattern and two as X-linked recessives.

Treatment Options

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References

Naeem MA, Chavali VR, Ali S, Iqbal M, Riazuddin S, Khan SN, Husnain T, Sieving PA, Ayyagari R, Riazuddin S, Hejtmancik JF, Riazuddin SA. GNAT1 associated with Autosomal Recessive Congenital Stationary Night Blindness. Invest Ophthalmol Vis Sci. 2011 Dec 21. [Epub ahead of print]

PubMed ID: 
22190596

Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010 Sep;29(5):335-75.

PubMed ID: 
20362068

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.

PubMed ID: 
8673138