scholarly journals A Novel Heterozygous Missense Mutation in GNAT1 Leads to Autosomal Dominant Riggs Type of Congenital Stationary Night Blindness

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Christina Zeitz ◽  
Cécile Méjécase ◽  
Mathilde Stévenard ◽  
Christelle Michiels ◽  
Isabelle Audo ◽  
...  
Keyword(s):  
Binding Site ◽  
Night Blindness ◽  
Autosomal Dominant ◽  
Protein Localization ◽  
Cone Dystrophy ◽  
Congenital Stationary Night Blindness ◽  
Gtp Binding ◽  
Novel Variant ◽  
Localization Signal ◽  
Phototransduction Cascade

Autosomal dominant congenital stationary night blindness (adCSNB) is rare and results from altered phototransduction giving a Riggs type of electroretinogram (ERG) with loss of the rod a-wave and small b-waves. These patients usually have normal vision in light. Only few mutations in genes coding for proteins of the phototransduction cascade lead to this condition; most of these gene defects cause progressive rod-cone dystrophy. Mutation analysis of an adCSNB family with a Riggs-type ERG revealed a novel variant (c.155T>A p.Ile52Asn) in GNAT1 coding for the α-subunit of transducin, cosegregating with the phenotype. Domain predictions and 3D-modelling suggest that the variant does not affect the GTP-binding site as other GNAT1 adCSNB mutations do. It affects a predicted nuclear localization signal and a part of the first α-helix, which is distant from the GTP-binding site. The subcellular protein localization of this and other mutant GNAT1 proteins implicated in CSNB are unaltered in mammalian GNAT1 overexpressing cells. Our findings add a third GNAT1 mutation causing adCSNB and suggest that different pathogenic mechanisms may cause this condition.

scholarly journals Comprehensive Geno- and Phenotyping in a Complex Pedigree Including Four Different Inherited Retinal Dystrophies

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 137
Author(s):  
Johannes Birtel ◽  
Martin Gliem ◽  
Kristina Hess ◽  
Theresa H. Birtel ◽  
Frank G. Holz ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Night Blindness ◽  
Molecular Genetic ◽  
Cone Dystrophy ◽  
Molecular Testing ◽  
Congenital Stationary Night Blindness ◽  
Molecular Genetic Testing ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Novel Variant

Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.

scholarly journals Cone dystrophy and ectopic synaptogenesis in a Cacna1f loss of function model of congenital stationary night blindness (CSNB2A)

Channels ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 17-33 ◽  
Author(s):  
D. M. Waldner ◽  
N. C. Giraldo Sierra ◽  
S. Bonfield ◽  
L. Nguyen ◽  
I. S. Dimopoulos ◽  
...  
Keyword(s):  
Night Blindness ◽  
Cone Dystrophy ◽  
Congenital Stationary Night Blindness ◽  
Loss Of Function ◽  
Function Model

Congenital Stationary Night Blindness: Pathophysiology, Signs, Diagnosis, and Treatment

2021 ◽  
pp. 155-158
Keyword(s):  
Molecular Genetics ◽  
Night Blindness ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Common Type ◽  
Diagnosis And Treatment ◽  
Recessive Trait ◽  
Congenital Stationary Night Blindness ◽  
Dominant Inheritance ◽  
Retinal Disorder

Congenital stationary night blindness (CSNB) is a nonprogressive inherited retinal disorder characterized by lifelong night blindness. The Schubert-Bornschein type is the most common type of CSNB. The disease is most commonly inherited as an X-linked recessive trait, but can also have an autosomal recessive and rarely autosomal dominant inheritance. Clinical, electrophysiological, and molecular genetics about CSNB are reviewed in this paper.

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

1999 ◽  
Vol 13 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Najma al-Jandal ◽  
G. Jane Farrar ◽  
Anna-Sophia Kiang ◽  
Marian M. Humphries ◽  
Noreen Bannon ◽  
...  
Keyword(s):  
Night Blindness ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Congenital Stationary Night Blindness ◽  
Rhodopsin Gene

scholarly journals Überblick über die kongenitale stationäre Nachtblindheit mit überwiegend normalem Fundus

2018 ◽  
Vol 235 (03) ◽  
pp. 281-289 ◽  
Author(s):  
Christina Zeitz ◽  
Christoph Friedburg ◽  
Markus Preising ◽  
Birgit Lorenz
Keyword(s):  
Night Blindness ◽  
Autosomal Dominant ◽  
Congenital Stationary Night Blindness

ZusammenfassungKongenitale stationäre Nachtblindheit (Englisch: congenital stationary night blindness, CSNB) bezeichnet eine klinisch und genetisch unterscheidbare Gruppe von nicht progressiven Netzhauterkrankungen, die kaum Fundusauffälligkeiten zeigt. Die Vererbung kann autosomal-dominant (adCSNB), autosomal-rezessiv (arCSNB) oder X-chromosomal (XLCSNB) sein. Weitere klinische Merkmale können Myopie, Hyperopie, Strabismus, Nystagmus und reduzierter Visus sein. Mittels Elektroretinografie kann eine Riggs- und eine Schubert-Bornschein-Form unterschieden werden. Während die Riggs-Form eine Fehlfunktion der Stäbchen selbst aufweist, zeigen Patienten mit der weitaus häufigeren Schubert-Bornschein-Form eine Signalübertragungsstörung zwischen den Photorezeptoren und nachgeschalteten Bipolarzellen. Die Schubert-Bornschein-Form der CSNB lässt sich anhand des Elektroretinogramms (ERG) noch weiter in eine inkomplette (Englisch: incomplete, icCSNB) und komplette Form (Englisch: complete, cCSNB) einteilen. Während es sich bei der cCSNB um eine Fehlfunktion des ON-Signalwegs handelt, sind bei der icCSNB sowohl der ON- als auch der OFF-Signalweg und damit meist auch die Sehschärfe betroffen. Mittels klassischer Kopplungsanalyse, Kandidatengenanalyse und seit Neuerem Hochdurchsatzsequenzierung konnten bisher Mutationen in 13 verschiedenen Genen mit dieser Erkrankung assoziiert werden. Durch Studien an Zelllinien oder Tiermodellen konnte gezeigt werden, dass der Phänotyp der Patienten mit der Expression, Proteinlokalisation und Funktion der entsprechenden Moleküle korreliert: Gene, die bei Patienten mit der Riggs-Form der CSNB mutiert sind, haben eine bedeutende Rolle in der Phototransduktionskaskade der Stäbchen. Gene, die bei Patienten mit der icCSNB mutiert sind, kodieren für Proteine, die für die Freisetzung des Neurotransmitters Glutamat am synaptischen Spalt der Photorezeptoren verantwortlich sind. Gene, die bei Patienten mit der cCSNB mutiert sind, kodieren für Proteine, die für die Aufnahme des Glutamats und Weiterleitung des Signals an den ON-Bipolarzellen verantwortlich sind. Erste Therapieversuche im Tiermodell zeigen, dass die CSNB mittels eines gentherapeutischen Ansatzes geheilt werden könnte. Die CSNB betreffende Studien sind einerseits wichtig für eine genaue Diagnose für den Patienten, andererseits helfen sie bei der Entschlüsselung der Moleküle, die für die Signalübertragung zwischen Photorezeptoren und Bipolarzellen eine Rolle spielen, ein bislang wenig erforschtes Gebiet.

scholarly journals Genetic testing for congenital stationary night blindness

2017 ◽  
Vol 1 (s1) ◽  
pp. 38-40
Author(s):  
Andi Abeshi ◽  
Pamela Coppola ◽  
Tommaso Beccari ◽  
Munis Dundar ◽  
Francesco Viola ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Night Blindness ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Scientific Literature ◽  
Genetic Test ◽  
Clinical Findings ◽  
Ophthalmological Examination ◽  
Congenital Stationary Night Blindness ◽  
Autosomal Recessive Manner

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for congenital stationary night blindness (CSNB). CSNB is inherited in an autosomal dominant manner in the case of mutations in the GNAT1, PDE6B and RHO genes, in an autosomal recessive manner in the case of mutations in the CABP4, GNB3, GPR179, GRM6, LRIT3, SAG, SLC24A1, TRPM1 and genes and in an X-linked recessive manner in the case of mutations in the CACNA1F and NYX genes. The overall prevalence of CSNB is not known. Clinical diagnosis is based on clinical findings, ophthalmological examination, visual evoked potentials and electroretinography. The genetic test is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

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