Nature Genetics
19, 264 - 267 (1998)
doi:10.1038/947
Loss-of-function mutations in a calcium-channel  1-subunit
gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness
N. Torben Bech-Hansen1, Margaret J. Naylor1, Tracy A. Maybaum1, William G. Pearce1, 2, Ben Koop3, Gerald A. Fishman4, Marilyn Mets5, Maria A. Musarella6
& Kym M. Boycott11
Department of Medical Genetics, University of Calgary,
Calgary, Alberta, Canada T2N 4N1. 2
Department of Ophthalmology, University of Alberta,
Edmonton, Alberta, Canada T6G2G3. 3
Department of Biology, University of Victoria,
Victoria, British Columbia, Canada V8W 2Y2. 4
Department of Ophthalmology, University of Illinois,
Chicago, Illinois 60612, USA. 5
Department of Ophthalmology, Children's Memorial Hospital,
Chicago, Illinois 60614, USA. 6
Departments of Ophthalmology, University of Toronto
, Toronto, Ontario, Canada, and
Long Island College Hospital, Brooklyn, New York
11201, USA.
Correspondence should be addressed to N. Torben Bech-Hansen ntbech@acs.ucalgary.caX-linked congenital stationary night blindness (CSNB) is a recessive
non-progressive retinal disorder characterized by night blindness, decreased
visual acuity, myopia, nystagmus and strabismus1,
2,
3. Two
distinct clinical entities of X-linked CSNB have been proposed4.
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  1-subunit genes.
Mutation analysis of this new 1-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.
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