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DM Hunt, S Johnson, S Halford, AM Morris, R Patel, K Zhang, A Hardcastle, AT Moore; Genomic Structure and Pattern of Alternate Splicing for RIM1, a Candidate Gene for CORD7 . Invest. Ophthalmol. Vis. Sci. 2002;43(13):838.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The RIM1 gene is a member of the NIM/RIM family of neuronal C2-domain proteins. It encodes a protein of 1686 amino acids and functions as a Rab3 Interacting Molecule. It has so far only been described as a cDNA in rat. The gene is expressed in the brain and in the photoreceptors of the retina where it is localized to the pre-synaptic ribbons in ribbon synapses. The gene maps to chromosome 6p within the region for CORD7 delineated by linkage. It is therefore a good candidate gene for this disease. Methods: The genomic structure of the gene has been determined by a combination of in silico sequence comparisons, retinal cDNA library screening, and RT-PCR from retinal mRNA. Mutation screening was carried out by the direct sequencing of PCR products derived from each exon of the gene. Results: The exon/intron structure of the human gene has been determined. It consists of 35 exons and stretches over approximately 494 kb of genomic DNA. The extent of alternate splicing of the human retinal transcript has been examined in detail. Alternate splicing appears to be confined to exons 21 to 29, although exon 24 which encodes a SH3-binding domain is always present. Mutation screening of all 35 exons of the gene in our CORD7 family has identified a missense mutation; this change was absent from the RIM1 gene in over 100 normal individuals. Conclusion: The pattern of alternate splicing of the RIM1 transcript in the human retina has been fully determined. The identified mutation results in an amino acid substitution in one of the C2-domains of the protein. This site is conserved in the rat sequence, the only other sequence available at present. The nature of mutation and its absence from over 100 normal individuals suggests that it is probably disease-causing.
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