Abstract
Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B (rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram (ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.
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Acknowledgements
We thank all members of CORD5 families and acknowledge E Blennow for collecting blood samples and J Moharer for technical assistance. This study was supported by Grants from Visare Norr and University Hospital of Umeå.
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The accession numbers and URLs for data presented herein are as follows: Information on CORD5–entity can be found on Online Mendelian Inheritance in Man (OMIM) – http://www.ncbi.nlm.nih.gov/OMIM. Primer design was performed using program available on http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi. Genomic sequence of the PITPNM3 gene is available on http://www.ensembl.org (ENSG00000091622).
ClustalW 1.74 multiple sequence alignment program – http://www.ebi.ac.uk/clustalw/.
To sort intolerant from tolerant amino acid substitutions – http://blocks.fhcrc.org and to check possible impact of an amino acid substitution on the structure and function of a human protein was used PolyPhen analys program – http://coot.embl.de/PolyPhen/.
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Köhn, L., Kadzhaev, K., Burstedt, M. et al. Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families. Eur J Hum Genet 15, 664–671 (2007). https://doi.org/10.1038/sj.ejhg.5201817
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DOI: https://doi.org/10.1038/sj.ejhg.5201817
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