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R. Jalkanen, C. Saloranta, T. Alitalo, E.-M. Sankila; Novel Mutation and Alternative Splicing of CACNA1F Gene. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1301.
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© ARVO (1962-2015); The Authors (2016-present)
X-linked congenital stationary night blindness (CSNBX) is a nonprogressive retinal disease characterized by impaired night vision, myopia, nystagmus, strabismus, and reduced visual acuity. According to ERG findings, CSNBX is divided into complete type (CSNB1) and incomplete type (CSNB2). CSNB1 is caused by mutations in the NYX gene (Xp11.4), whereas CSNB2 results from mutations in the L-type calcium channel alpha1-subunit gene, CACNA1F (Xp11.23). The purpose of this study was to determine the mutation underlying the phenotype of a Finnish patient with congenital nystagmus, reduced visual acuity, progressive myopia, and pale optic discs and ocular fundi.
All 48 exons and flanking intronic regions of the CACNA1F gene were analyzed by direct sequencing. Presence of the identified mutation among control samples was studied with HpyCH4III restriction endonuclease analysis. The exon 14-18 region of CACNA1F mRNA from cultured lymphoblasts was analyzed by RT-PCR and cDNA sequencing.
A novel CACNA1F mutation, IVS16+2T>C, was present in the patient and a carrier female, but absent from 100 controls. RT-PCR analysis of lymphoblast RNA from the patient revealed an aberrant splicing product predicting in-frame deletion/insertion into the encoded channel protein. Control sample showed a wt transcript that contained all the exons 14-18, and several alternative splice variants predicting in-frame deletion/insertion or premature termination codons.
Mutations in CACNA1F are known to cause CSNB2. Some patients may, however, show divergent but overlapping phenotypes, including retinal and optic disc atrophy, Åland Island eye disease, and progressive cone-rod dystrophy. The phenotype of our patient was consistent with CSNB2, although it had features from both Åland Island eye disease and progressive cone-rod dystrophy. Several alternative CACNA1F splice variants were present in lymphoblasts suggesting that alternative splicing enhances the channel diversity or regulates the channel expression.
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