Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

doi:10.1016/j.preteyeres.2014.09.001

Progress in Retinal and Eye Research

Volume 45, March 2015, Pages 58-110

https://doi.org/10.1016/j.preteyeres.2014.09.001 Get rights and content

Abstract

Congenital stationary night blindness (CSNB) refers to a group of genetically and clinically heterogeneous retinal disorders. Seventeen different genes with more than 360 different mutations and more than 670 affected alleles have been associated with CSNB, including genes coding for proteins of the phototransduction cascade, those important for signal transmission from the photoreceptors to the bipolar cells or genes involved in retinoid recycling in the retinal pigment epithelium. This article describes the phenotypic characteristics of different forms of CSNB that are necessary for accurate diagnosis and to direct and improve genetic testing. An overview of classical and recent methods used to identify specific CSNB genotypes is provided and a meta-analysis of all previously published and novel data is performed to determine the prevalence of disease-causing mutations. Studies of the underlying molecular pathogenic mechanisms based on cell culture techniques and animal studies are outlined. The article highlights how the study of CSNB has increased understanding of the mechanisms of visual signalling in the retina, likely to prove important in developing future treatments for CSNB and other retinal disorders.

Introduction

Congenital stationary night blindness (CSNB) refers to a genetically determined largely non-progressive group of retinal disorders that predominantly affect signal processing within photoreceptors, retinoid recycling in the retinal pigment epithelium (RPE) or signal transmission via retinal bipolar cells (Zeitz, 2007). CSNB is clinically and genetically heterogeneous. Patients often complain of night or dim light vision disturbance or delayed dark adaptation, but photophobia is also reported in a subgroup of patients. Some forms may be associated with other ocular signs such as poor visual acuity, myopia, nystagmus, strabismus and fundus abnormalities (Zeitz, 2007). The night vision disturbance may be overlooked since it is highly subjective especially for individuals living in an urban or well-lit environment. Vision problems may also be denied (Dryja, 2000). Scotopic vision is rarely tested routinely and CSNB is likely under-diagnosed by clinicians, confounding estimates of prevalence.

To our knowledge, the first individuals diagnosed with CSNB were the descendants of Jean Nougaret, who was born 1637 in southern France. Since then many clinicians and researchers have contributed to the understanding of different CSNB phenotypes, genetic causes and pathogenic mechanisms. The purpose of this article is to summarise these findings and to extend current knowledge by inclusion of novel data and interpretation.

Section snippets

Clinical classification

CSNB can be subdivided according to the pattern of inheritance which may be X-linked, autosomal recessive or autosomal dominant (see also: 3. CSNB genes and mutations). Fundus appearance may be normal or abnormal but in all cases the full field electroretinogram (FF-ERG) is critical for functional phenotyping and precise diagnosis.

Gene identification strategies

CSNB is a group of genetically and clinically heterogeneous retinal disorders caused by mutations in seventeen identified genes (Table 1) with an unknown number yet to be identified. Genes mutated in patients with CSNB have been identified by different methods including classical linkage analysis with a combination of candidate gene and positional cloning approaches, autozygosity mapping, pure candidate gene approaches as well as by whole exome sequencing (WES).

Classical linkage approaches have

Animal models for CSNB

Animal models have been shown to be an excellent tool to identify and to elucidate the pathogenic mechanism of gene defects underlying CSNB. In addition, well characterized animal models are crucial to develop pharmaceutical or genetic treatments. In Table 4 we summarize more than 30 animal models of CSNB. Most are mouse models, but for some gene defects other species including zebrafish, rat, dog and horse have been described. We provide the gene defect with the respective accession number if

Molecules important in the phototransduction cascade and retinoid recycling (RHO, GNAT1, PDE6B, SLC24A1, RDH5, RPE65, RLBP1, GRK1 and SAG)

Several forms of CSNB are caused by mutations that affect molecules of the phototransduction cascade or retinoid recycling and these are highlighted in Fig. 11. Rhodopsin (RHO), a seven transmembrane G-protein coupled receptor represents the light-sensitive pigment of rod photoreceptors, which consists of the 11-cis-aldehyde of vitamin A (11-cis-retinal) bound covalently to opsin. Upon absorption of a photon by the rods, the chromophore is converted to its all-trans isomer and subsequently RHO

Summary and future perspectives

An important first step in the genetic investigation of CSNB is comprehensive phenotyping. Phenotypic characterisation may suggest genes that encode pre- or postsynaptic proteins to be good candidates (Fig. 11, Fig. 14). A “Riggs-type” ERG (marked scotopic ERG a-wave reduction; see Section 2.2.1) may prompt investigation of molecules and novel mutations that affect phototransduction or retinoid recycling whereas an electronegative (“Schubert-Bornshein-type”) ERG (scotopic ERG a-wave normal and

CSNB consortium

Tharigopala Arokiasamy, Mario Anastasi, Claire Audier, Eyal Banin, Wolfgang Berger, Elfride De Baere, Shomi S. Bhattacharya, Rebecca Bellone, Béatrice Bocquet, Dominique Bonneau, Kinga Bujakowska, Ingele Casteels, Sabine Defoort-Dhellemmes, Miguel Dias, Hélène Dollfus, Isabelle Drumare, Said El Shamieh, Christoph Friedburg, Irene Gottlob, Cyril Goudet, Christian P. Hamel, John R. Heckenlively, Elise Héon, Graham E Holder, Samuel G. Jacobson, Bernhard Jurklies, Josseline Kaplan, Ulrich Kellner,

Acknowledgments

We are thankful to all patients and family members who participated in this study. We acknowledge assistant engineers from CZ's previous laboratory at the Institute for Medical Genetics and Gene Diagnostics from the University in Zurich, Switzerland including Ursula Forster, Silke Feil and Mariana Wittmer and from the current laboratory at the Institut de la Vision in Paris, France including Marie-Elise Lancelot, Christelle Michiels, Vanessa Démontant, Christel Condroyer and Aline Antonio for

References (330)

K. Alpadi et al.
RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses
J. Biol. Chem.
(2008)
G. Arden et al.
S-cone ERGs elicited by a simple technique in normals and in tritanopes
Vis. Res.
(1999)
J. Arikkath et al.
Auxiliary subunits: essential components of the voltage-gated calcium channel complex
Curr. Opin. Neurobiol.
(2003)
I. Audo et al.
Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness
Am. J. Hum. Genet.
(2012)
I. Audo et al.
TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness
Am. J. Hum. Genet.
(2009)
I. Audo et al.
The negative ERG: clinical phenotypes and disease mechanisms of inner retinal dysfunction
Surv. Ophthalmol.
(2008)
W. Baehr et al.
Naturally occurring animal models with outer retina phenotypes
Vis. Res.
(2009)
E.L. Berson et al.
Paraneoplastic night blindness with malignant melanoma
Am. J. Ophthalmol.
(1988)
M.M. Bijveld et al.
Genotype and phenotype of 101 Dutch patients with congenital stationary night blindness
Ophthalmology
(2013)
K.M. Boycott et al.
Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F
Can. J. Ophthalmol.
(2000)

K.M. Boycott et al.

Evidence for genetic heterogeneity in X-linked congenital stationary night blindness

Am. J. Hum. Genet.

(1998)

V. Burtscher et al.

Spectrum of Cav1.4 dysfunction in congenital stationary night blindness type 2

Biochim. Biophys. Acta

(2014)

B. Chang et al.

Retinal degeneration mutants in the mouse

Vis. Res.

(2002)

T.P. Dryja

Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture

Am. J. Ophthalmol.

(2000)

G.D. Field et al.

Nonlinear signal transfer from mouse rods to bipolar cells and implications for visual sensitivity

Neuron

(2002)

P. Garriga et al.

The eye photoreceptor protein rhodopsin. Structural implications for retinal disease

FEBS Lett.

(2002)

C.A. Gurnett et al.

Dual function of the voltage-dependent Ca²⁺ channel alpha 2 delta subunit in current stimulation and subunit interaction

Neuron

(1996)

F. Haeseleer et al.

Calcium-binding proteins: intracellular sensors from the calmodulin superfamily

Biochem. Biophys. Res. Commun.

(2002)

J.R. Heckenlively et al.

Loss of electroretinographic oscillatory potentials, optic atrophy, and dysplasia in congenital stationary night blindness

Am. J. Ophthalmol.

(1983)

G.R. Abecasis et al.

A map of human genome variation from population-scale sequencing

Nature

(2010)

I.A. Adzhubei et al.

A method and server for predicting damaging missense mutations

Nat. Methods

(2010)

N. al-Jandal et al.

A novel mutation within the rhodopsin gene (Thr-94-Ile) causing autosomal dominant congenital stationary night blindness

Hum. Mutat.

(1999)

M.A. Aldahmesh et al.

A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype

Mol. Vis.

(2010)

K.R. Alexander et al.

‘On’ response defect in paraneoplastic night blindness with cutaneous malignant melanoma

Invest. Ophthalmol. Vis. Sci.

(1992)

D.M. Altshuler et al.

Integrating common and rare genetic variation in diverse human populations

Nature

(2010)

J. An et al.

Behavioral phenotypic properties of a natural occurring rat model of congenital stationary night blindness with Cacna1f mutation

J. Neurogenet.

(2012)

I. Audo et al.

The familial dementia gene revisited: a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal dominant retinal dystrophy in a large family

Hum. Mol. Genet.

(2014)

I. Audo et al.

Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

Orphanet J. Rare Dis.

(2012)

M. Azam et al.

A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family

Mol. Vis.

(2009)

R. Bahadori et al.

Nyctalopin is essential for synaptic transmission in the cone dominated zebrafish retina

Eur. J. Neurosci.

(2006)

S.L. Ball et al.

Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer

Invest. Ophthalmol. Vis. Sci.

(2002)

N.T. Bech-Hansen et al.

Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness

Nat. Genet.

(1998)

N.T. Bech-Hansen et al.

Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness

Nat. Genet.

(2000)

R.R. Bellone et al.

Association analysis of candidate SNPs in TRPM1 with leopard complex spotting (LP ) and congenital stationary night blindness (CSNB) in horses

Anim. Genet.

(2010)

R.R. Bellone et al.

Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus)

Genetics

(2008)

R.R. Bellone et al.

Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses

Brief. Funct. Genomics

(2010)

R.R. Bellone et al.

Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse

PLoS ONE

(2013)

W. Berger et al.

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB)

Hum. Genet.

(1995)

A. Bernstein et al.

Genetic ablation in transgenic mice

Mol. Biol. Med.

(1989)

M.M. Bijveld et al.

Assessment of night vision problems in patients with congenital stationary night blindness

PLoS ONE

(2013)

K.M. Boycott et al.

A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants

Hum. Genet.

(2001)

M.S. Burstedt et al.

Effects of prolonged dark adaptation in patients with retinitis pigmentosa of Bothnia type: an electrophysiological study

Doc. Ophthalmol.

(2008)

R.A. Bush et al.

A proximal retinal component in the primate photopic ERG a-wave

Invest. Ophthalmol. Vis. Sci.

(1994)

R.A. Bush et al.

Inner retinal contributions to the primate photopic fast flicker electroretinogram

J. Opt. Soc. Am. A Opt. Image Sci. Vis.

(1996)

P.D. Calvert et al.

Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha-subunit

Proc. Natl. Acad. Sci. U. S. A.

(2000)

Y. Cao et al.

Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons

Proc. Natl. Acad. Sci. U. S. A.

(2012)

Y. Cao et al.

TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner

J. Neurosci.

(2011)

R.E. Carr et al.

Oguchi's disease

Arch. Ophthalmol.

(1965)

R.E. Carr et al.

Rhodopsin kinetics and rod adaptation in Oguchi disease

Invest. Ophthalmol. Vis. Sci.

(1967)

L.D. Carter-Dawson et al.

Differential effect of the rd mutation on rods and cones in the mouse retina

Invest. Ophthalmol. Vis. Sci.

(1978)

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¹: Percentage of work contributed by each author in the production of the manuscript is as follows: Christina Zeitz: 70%; Anthony G. Robson: 10%; Isabelle Audo: 20%.

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Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

Abstract

Introduction

Section snippets

Clinical classification

Gene identification strategies

Animal models for CSNB

Molecules important in the phototransduction cascade and retinoid recycling (RHO, GNAT1, PDE6B, SLC24A1, RDH5, RPE65, RLBP1, GRK1 and SAG)

Summary and future perspectives

CSNB consortium

Acknowledgments

J. Biol. Chem.

Vis. Res.

Curr. Opin. Neurobiol.

Am. J. Hum. Genet.

Am. J. Hum. Genet.

Surv. Ophthalmol.

Vis. Res.

Am. J. Ophthalmol.

Ophthalmology

Can. J. Ophthalmol.

Am. J. Hum. Genet.

Biochim. Biophys. Acta

Vis. Res.

Am. J. Ophthalmol.

Neuron

FEBS Lett.

Neuron

Biochem. Biophys. Res. Commun.

Am. J. Ophthalmol.

A map of human genome variation from population-scale sequencing

Nature

A method and server for predicting damaging missense mutations

Nat. Methods

A novel mutation within the rhodopsin gene (Thr-94-Ile) causing autosomal dominant congenital stationary night blindness

Hum. Mutat.

A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype

Mol. Vis.

‘On’ response defect in paraneoplastic night blindness with cutaneous malignant melanoma

Invest. Ophthalmol. Vis. Sci.

Integrating common and rare genetic variation in diverse human populations

Nature

Behavioral phenotypic properties of a natural occurring rat model of congenital stationary night blindness with Cacna1f mutation

J. Neurogenet.

The familial dementia gene revisited: a missense mutation revealed by whole-exome sequencing identifies ITM2B as a candidate gene underlying a novel autosomal dominant retinal dystrophy in a large family

Hum. Mol. Genet.

Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

Orphanet J. Rare Dis.

A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family

Mol. Vis.

Nyctalopin is essential for synaptic transmission in the cone dominated zebrafish retina

Eur. J. Neurosci.

Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer

Invest. Ophthalmol. Vis. Sci.

Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness

Nat. Genet.

Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness

Nat. Genet.

Association analysis of candidate SNPs in TRPM1 with leopard complex spotting (LP ) and congenital stationary night blindness (CSNB) in horses

Anim. Genet.

Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus)

Genetics

Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses

Brief. Funct. Genomics

Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse

PLoS ONE

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB)

Hum. Genet.

Genetic ablation in transgenic mice

Mol. Biol. Med.

Assessment of night vision problems in patients with congenital stationary night blindness

PLoS ONE

A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants

Hum. Genet.

Effects of prolonged dark adaptation in patients with retinitis pigmentosa of Bothnia type: an electrophysiological study

Doc. Ophthalmol.

A proximal retinal component in the primate photopic ERG a-wave

Invest. Ophthalmol. Vis. Sci.

Inner retinal contributions to the primate photopic fast flicker electroretinogram

J. Opt. Soc. Am. A Opt. Image Sci. Vis.