Mutations in the gene KCNV2 encoding a voltage-gated potassium channel subunit cause "cone dystrophy with supernormal rod electroretinogram" in humans

Am J Hum Genet. 2006 Sep;79(3):574-9. doi: 10.1086/507568. Epub 2006 Jul 24.

Abstract

"Cone dystrophy with supernormal rod electroretinogram (ERG)" is an autosomal recessive disorder that causes lifelong visual loss combined with a supernormal ERG response to a bright flash of light. We have linked the disorder to a 0.98-cM (1.5-Mb) region on chromosome 9p24, flanked by rs1112534 and rs1074449, using homozygosity mapping in one large consanguineous pedigree. Analysis of one gene within this region, KCNV2, showed a homozygous nonsense mutation. Mutations were also found in 17 alleles of 10 other unrelated families with the same disorder. In situ hybridization demonstrated KCNV2 expression in human rod and cone photoreceptors. The precise function of KCNV2 in human photoreceptors remains to be determined, although this work suggests that mutations might perturb or abrogate I(KX), the potassium current within vertebrate photoreceptor inner segments, which has been shown to set their resting potential and voltage response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 9 / genetics
  • Codon, Nonsense
  • Electroretinography
  • Female
  • Homozygote
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Physical Chromosome Mapping
  • Potassium Channels, Voltage-Gated / chemistry
  • Potassium Channels, Voltage-Gated / genetics*
  • Protein Structure, Tertiary
  • RNA, Messenger / analysis
  • Retinal Cone Photoreceptor Cells / chemistry
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / chemistry
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*

Substances

  • Codon, Nonsense
  • KCNV2 protein, human
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger