Mutations in CACNA2D4 Cause Distinctive Retinal Dysfunction in Humans

Abstract

CACNA2D4 (NM_172364) encodes the α2δ4 subunit of the photoreceptor voltage-gated calcium channels (Cav1.4), which modulate glutamate release from the photoreceptors to the bipolar cells. 1 Dolphin A.C. The α2δ subunits of voltage-gated calcium channels. Biochim Biophys Acta. 2013; 1828: 1541-1549 Crossref PubMed Scopus (143) Google Scholar CACNA2D4 mutations have been associated with a rare recessive retinal cone dystrophy (RCD4, OMIM #610478), 2 Wycisk K.A. Zeitz C. Feil S. et al. Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy. Am J Hum Genet. 2006; 79: 973-977 Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar first described in 2 adult siblings with a homozygous truncating mutation in exon 25 of CACNA2D4: c.[2406C>A] (p.[Tyr802*]) associated with mildly reduced visual acuity (VA), photophobia, foveal pigment mottling, an electronegative scotopic electroretinogram (ERG) and markedly subnormal cone responses. 2 Wycisk K.A. Zeitz C. Feil S. et al. Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy. Am J Hum Genet. 2006; 79: 973-977 Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar The second report described a homozygous deletion of exons 17-26 of CACNA2D4 associated with mildly reduced VA, photophobia, normal retinal imaging, normal scotopic ERG, and mildly reduced cone responses (Vincent A, et al. Non-truncating homozygous deletion in CACNA2D4 mimicking oligocone trichromacy. Poster, ARVO 2014, Orlando, FL). The third report suggested a cone–rod dystrophy caused by a homozygous mutation: c.[2120G>A], (p.[Arg707His]). 3 Huang X.F. Huang F. Wu K.C. et al. Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing. Genet Med. 2015; 17: 271-278 Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar