title: Mutations in TRPM1 are a common cause of complete congenital stationary night blindness.
abstract: Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impaired night vision and variable decreased visual acuity. We report here that six out of eight female probands with autosomal-recessive complete CSNB (cCSNB) had mutations in TRPM1, a retinal transient receptor potential (TRP) cation channel gene. These data suggest that TRMP1 mutations are a major cause of autosomal-recessive CSNB in individuals of European ancestry. We localized TRPM1 in human retina to the ON bipolar cell dendrites in the outer plexifom layer. Our results suggest that in humans, TRPM1 is the channel gated by the mGluR6 (GRM6) signaling cascade, which results in the light-evoked response of ON bipolar cells. Finally, we showed that detailed electroretinography is an effective way to discriminate among patients with mutations in either TRPM1 or GRM6, another autosomal-recessive cCSNB disease gene. These results add to the growing importance of the diverse group of TRP channels in human disease and also provide new insights into retinal circuitry.
authors.affiliation: Bartiméus, Institute for the Visually Impaired, 3702 AD Zeist, The Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Mieke M C
authors.initials: MM
authors.lastname: Bijveld
authors.forename: Yvonne B
authors.initials: YB
authors.lastname: Claassen
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Pearring
authors.forename: Francoise M
authors.initials: FM
authors.lastname: Meire
authors.forename: Maureen A
authors.initials: MA
authors.lastname: McCall
authors.forename: Frans C C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gregg
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Maarten
authors.initials: M
authors.lastname: Kamermans
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002872:Chromosome Deletion; D015331:Cohort Studies; D004596:Electroretinography / Q000592:standards; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009755:Night Blindness / Q000151:congenital* / Q000235:genetics* / Q000503:physiopathology; D009679:Nuclear Family; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D050053:TRPM Cation Channels; C492059:TRPM1 protein, human