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A Mutation in SLC24A1 Implicated in Autosomal-Recessive Congenital Stationary Night Blindness |
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| Authors: | S Amer Riazuddin Amber Shahzadi Zubair M Ahmed Radha Ayyagari Virgilio G Ponferrada Christelle Michiels Marie-Elise Lancelot Idrees A Nasir Shaheen N Khan Xiaodong Jiao Sheikh Riazuddin Paul A Sieving J Fielding Hejtmancik |
| Institution: | 1 National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan 2 The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA 3 INSERM, U968, Paris F-75012, France 4 CNRS, UMR_7210 Paris F-75012, France 5 Department of Genetics, Institut de la Vision, UPMC Univ Paris 06, UMR_S 968, Paris, F-75012, France 6 Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA 7 Department of Ophthalmology, College of Medicine, Cincinnati, OH 45229, USA 8 Shiley Eye Center, University of California, San Diego, La Jolla, CA 92037, USA 9 Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris F-75012, France 10 Department of Molecular Genetics, Institute of Ophthalmology, London EC1V 9EL, UK 11 Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 21850, USA 12 Department of Ophthalmology, The University of Alberta, Edmonton, AB T5H 3V9 Canada 13 Allama Iqbal Medical College, Lahore 54550, Pakistan 14 Center for Human Disease Modeling, Duke University, Durham, NC 27710, USA |
| Abstract: | Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder that can be associated with impaired night vision. The last decade has witnessed huge progress in ophthalmic genetics, including the identification of three genes implicated in the pathogenicity of autosomal-recessive CSNB. However, not all patients studied could be associated with mutations in these genes and thus other genes certainly underlie this disorder. Here, we report a large multigeneration family with five affected individuals manifesting symptoms of night blindness. A genome-wide scan localized the disease interval to chromosome 15q, and recombination events in affected individuals refined the critical interval to a 10.41 cM (6.53 Mb) region that harbors SLC24A1, a member of the solute carrier protein superfamily. Sequencing of all the coding exons identified a 2 bp deletion in exon 2: c.1613_1614del, which is predicted to result in a frame shift that leads to premature termination of SLC24A1 (p.F538CfsX23) and segregates with the disorder under an autosomal-recessive model. Expression analysis using mouse ocular tissues shows that Slc24a1 is expressed in the retina around postnatal day 7. In situ and immunohistological studies localized both SLC24A1 and Slc24a1 to the inner segment, outer and inner nuclear layers, and ganglion cells of the retina, respectively. Our data expand the genetic basis of CSNB and highlight the indispensible function of SLC24A1 in retinal function and/or maintenance in humans. |
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