TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness.
Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in approximately 60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.
Audo
Isabelle
I
INSERM, UMR_S968, F-75012, Paris, France.
Kohl
Susanne
S
Leroy
Bart P
BP
Munier
Francis L
FL
Guillonneau
Xavier
X
Mohand-Saïd
Saddek
S
Bujakowska
Kinga
K
Nandrot
Emeline F
EF
Lorenz
Birgit
B
Preising
Markus
M
Kellner
Ulrich
U
Renner
Agnes B
AB
Bernd
Antje
A
Antonio
Aline
A
Moskova-Doumanova
Veselina
V
Lancelot
Marie-Elise
ME
Poloschek
Charlotte M
CM
Drumare
Isabelle
I
Defoort-Dhellemmes
Sabine
S
Wissinger
Bernd
B
Léveillard
Thierry
T
Hamel
Christian P
CP
Schorderet
Daniel F
DF
De Baere
Elfride
E
Berger
Wolfgang
W
Jacobson
Samuel G
SG
Zrenner
Eberhart
E
Sahel
José-Alain
JA
Bhattacharya
Shomi S
SS
Zeitz
Christina
C
D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009755:Night Blindness / Q000151:congenital* / Q000235:genetics* / Q000503:physiopathology; D009679:Nuclear Family; D010375:Pedigree; D050053:TRPM Cation Channels / Q000235:genetics*
D050053:TRPM Cation Channels; C492059:TRPM1 protein, human