title: TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness.
abstract: 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.
authors.affiliation: INSERM, UMR_S968, F-75012, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.forename: Saddek
authors.initials: S
authors.lastname: Mohand-Saïd
authors.forename: Kinga
authors.initials: K
authors.lastname: Bujakowska
authors.forename: Emeline F
authors.initials: EF
authors.lastname: Nandrot
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.forename: Markus
authors.initials: M
authors.lastname: Preising
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kellner
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Renner
authors.forename: Antje
authors.initials: A
authors.lastname: Bernd
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.forename: Veselina
authors.initials: V
authors.lastname: Moskova-Doumanova
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Lancelot
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Poloschek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Drumare
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort-Dhellemmes
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Thierry
authors.initials: T
authors.lastname: Léveillard
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
mesh_terms: 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*
chemical_list: D050053:TRPM Cation Channels; C492059:TRPM1 protein, human