An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness

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Abstract

The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific calcium channel α1-subunit gene (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and showing high homology to L-type calcium channel α1–subunits. Mutation analysis in 13 families with CSNB2 revealed nine different mutations in 10 families, including three nonsense and one frameshift mutation. These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2.

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Figure 1: Physical mapping of CACNA1F.
Figure 2: CACNA1F encodes the α1-subunit of an L-type calcium channel.
Figure 3: Retinal specificity of CACNA1F.
Figure 4: RNA in situ hybridization.
Figure 5: Mutation analysis in family xlCSNB14.

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GenBank/EMBL/DDBJ

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Acknowledgements

We are grateful to the families who participated in this study. We thank B. Wissinger and M. Andrassi for sending DNA samples, K.B. Jedele for extensive help in manuscript preparation and H. Achatz for technical assistance. The work was supported by the German Federal Ministery for Education, Research and Technology by a grant to A.R. and A.M. as well as by Deutsche Retinitis Pigmentosa Gesellschaft by a grant to N.G.

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Correspondence to Alfons Meindl.

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