Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness
| Autor: | Marilyn B. Mets, Kym M. Boycott, Pearce Wg, Maria A. Musarella, Margaret J. Naylor, Fishman Ga, N. T. Bech-Hansen, Tracy A. Maybaum, Ben F. Koop |
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| Rok vydání: | 1998 |
| Předmět: |
Male
DNA Complementary X Chromosome Retinal Disorder Calcium Channels L-Type genetic structures Molecular Sequence Data Biology chemistry.chemical_compound Channelopathy Night Blindness Genetics medicine Humans Tissue Distribution Amino Acid Sequence TRPM1 Congenital stationary night blindness Base Sequence Genetic heterogeneity Retinal Exons medicine.disease eye diseases Pedigree chemistry Mutation Female Calcium Channels sense organs X-linked congenital stationary night blindness Nyctalopin |
| Zdroj: | Nature Genetics. 19:264-267 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/947 |
| Popis: | 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 alpha1-subunit genes. Mutation analysis of this new alpha1-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. |
| Databáze: | OpenAIRE |
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