Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness.
Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway. Mutations in NYX, GRM6, and TRPM1, expressed in the outer plexiform layer (OPL) lead to disruption of the ON-bipolar cell response and have been seen in patients with cCSNB. Whole-exome sequencing in cCSNB patients lacking mutations in the known genes led to the identification of a homozygous missense mutation (c.1807C>T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs(∗)57]) in a simplex male cCSNB patient. Additional screening with Sanger sequencing of 40 patients identified three other cCSNB patients harboring additional allelic mutations in GPR179. Although, immunhistological studies revealed Gpr179 in the OPL in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and Müller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated.
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Isabelle
I
Audo
Kinga
K
Bujakowska
Elise
E
Orhan
Charlotte M
CM
Poloschek
Sabine
S
Defoort-Dhellemmes
Isabelle
I
Drumare
Susanne
S
Kohl
Tien D
TD
Luu
Odile
O
Lecompte
Eberhart
E
Zrenner
Marie-Elise
ME
Lancelot
Aline
A
Antonio
Aurore
A
Germain
Christelle
C
Michiels
Claire
C
Audier
Mélanie
M
Letexier
Jean-Paul
JP
Saraiva
Bart P
BP
Leroy
Francis L
FL
Munier
Saddek
S
Mohand-Saïd
Birgit
B
Lorenz
Christoph
C
Friedburg
Markus
M
Preising
Ulrich
U
Kellner
Agnes B
AB
Renner
Veselina
V
Moskova-Doumanova
Wolfgang
W
Berger
Bernd
B
Wissinger
Christian P
CP
Hamel
Daniel F
DF
Schorderet
Elfride
E
De Baere
Dror
D
Sharon
Eyal
E
Banin
Samuel G
SG
Jacobson
Dominique
D
Bonneau
Xavier
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Zanlonghi
Guylene
G
Le Meur
Ingele
I
Casteels
Robert
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Koenekoop
Vernon W
VW
Long
Francoise
F
Meire
Katrina
K
Prescott
Thomy
T
de Ravel
Ian
I
Simmons
Hoan
H
Nguyen
Hélène
H
Dollfus
Olivier
O
Poch
Thierry
T
Léveillard
Kim
K
Nguyen-Ba-Charvet
José-Alain
JA
Sahel
Shomi S
SS
Bhattacharya
Christina
C
Zeitz
D000483:Alleles; D000818:Animals; D004596:Electroretinography / Q000379:methods; D059472:Exome; D015785:Eye Diseases, Hereditary; D005260:Female; D040181:Genetic Diseases, X-Linked; D018740:Genetic Heterogeneity; D060005:Genotyping Techniques / Q000379:methods; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D009216:Myopia / Q000235:genetics*; D009755:Night Blindness / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics; D012160:Retina / Q000002:abnormalities; D050053:TRPM Cation Channels / Q000235:genetics
C416505:NYX protein, human; D011509:Proteoglycans; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; C113897:metabotropic glutamate receptor 6