Mutations in TRPM1 are a common cause of complete congenital stationary night blindness

Am J Hum Genet. 2009 Nov;85(5):730-6. doi: 10.1016/j.ajhg.2009.10.012. Epub 2009 Nov 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Case-Control Studies
  • Chromosome Deletion
  • Cohort Studies
  • Electroretinography / standards
  • European Continental Ancestry Group / genetics
  • Exons
  • Female
  • Genes, Recessive
  • Heterozygote
  • Homozygote
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Mutation*
  • Mutation, Missense
  • Night Blindness / congenital*
  • Night Blindness / genetics*
  • Night Blindness / physiopathology
  • Nuclear Family
  • Retinal Rod Photoreceptor Cells / physiology
  • Signal Transduction
  • TRPM Cation Channels / genetics*

Substances

  • TRPM Cation Channels
  • TRPM1 protein, human