Referenced in: none

Automatically associated channels: Kir2.3 , Slo1

Title: Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy.

Authors: Katharina Agnes Wycisk, Christina Zeitz, Silke Feil, Mariana Wittmer, Ursula Forster, John Neidhardt, Bernd Wissinger, Eberhart Zrenner, Robert Wilke, Susanne Kohl, Wolfgang Berger

Journal, date & volume: Am. J. Hum. Genet., 2006 Nov , 79, 973-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17033974

Abstract
Retinal signal transmission depends on the activity of high voltage-gated l-type calcium channels in photoreceptor ribbon synapses. We recently identified a truncating frameshift mutation in the Cacna2d4 gene in a spontaneous mouse mutant with profound loss of retinal signaling and an abnormal morphology of ribbon synapses in rods and cones. The Cacna2d4 gene encodes an l-type calcium-channel auxiliary subunit of the alpha (2) delta type. Mutations in its human orthologue, CACNA2D4, were not yet known to be associated with a disease. We performed mutation analyses of 34 patients who received an initial diagnosis of night blindness, and, in two affected siblings, we detected a homozygous nucleotide substitution (c.2406C-->A) in CACNA2D4. The mutation introduces a premature stop codon that truncates one-third of the corresponding open reading frame. Both patients share symptoms of slowly progressing cone dystrophy. These findings represent the first report of a mutation in the human CACNA2D4 gene and define a novel gene defect that causes autosomal recessive cone dystrophy.