title: Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans.
abstract: Complete congenital stationary night blindness (cCSNB) is associated with loss of function of rod and cone ON bipolar cells in the mammalian retina. In humans, mutations in NYX and GRM6 have been shown to cause the condition. Through the analysis of a consanguineous family and screening of nine additional pedigrees, we have identified three families with recessive mutations in the gene TRPM1 encoding transient receptor potential cation channel, subfamily M, member 1, also known as melastatin. A number of other variants of unknown significance were found. All patients had myopia, reduced central vision, nystagmus, and electroretinographic evidence of ON bipolar cell dysfunction. None had abnormalities of skin pigmentation, although other skin conditions were reported. RNA derived from human retina and skin was analyzed and alternate 5' exons were determined. The most 5' exon is likely to harbor an initiation codon, and the protein sequence is highly conserved across vertebrate species. These findings suggest an important role of this specific cation channel for the normal function of ON bipolar cells in the human retina.
authors.affiliation: University College London (UCL) Institute of Ophthalmology, London EC1V 9EL, UK.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.forename: Donna S
authors.initials: DS
authors.lastname: Mackay
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Wright
authors.forename: Sophie
authors.initials: S
authors.lastname: Devery
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D015331:Cohort Studies; D003241:Consanguinity; D004596:Electroretinography; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009755:Night Blindness / Q000151:congenital* / Q000235:genetics*; D010375:Pedigree; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: D050053:TRPM Cation Channels; C492059:TRPM1 protein, human