Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness

N. Torben Bech-Hansen, Margaret J. Naylor, Tracy A. Maybaum, William G. Pearce, Ben Koop, Gerald A. Fishman, Marilyn B Mets, Maria A. Musarella, Kym M. Boycott

Research output: Contribution to journalArticlepeer-review

390 Scopus citations

Abstract

X-linked congenital stationary night blindness (CSNB) is a recessive non-progressive retinal disorder characterized by night blindness, decreased visual acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X-linked CSNB have been proposed. Patients with complete CSNB show moderate to severe myopia, undetectable rod function and a normal cone response, whereas patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but measurable rod and cone function. The electrophysiological and psychophysical features of these clinical entities suggest a defect in retinal neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects the recently described genetic heterogeneity in which the locus for complete CSNB (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the CSNB2 minimal region was characterized and found to have similarity to voltage-gated L-type calcium channel α1-subunit genes. Mutation analysis of this new α-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six different mutations that are all predicted to cause premature protein truncation. These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.

Original languageEnglish (US)
Pages (from-to)264-267
Number of pages4
JournalNature Genetics
Volume19
Issue number3
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Genetics

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