A Mutation in SLC24A1 Implicated in Autosomal-Recessive Congenital Stationary Night Blindness

• Published in: American journal of human genetics 2010-10, Vol.87 (4), p.523-531
• Main Authors: Riazuddin, S. Amer, Shahzadi, Amber, Zeitz, Christina, Ahmed, Zubair M., Ayyagari, Radha, Chavali, Venkata R.M., Ponferrada, Virgilio G., Audo, Isabelle, Michiels, Christelle, Lancelot, Marie-Elise, Nasir, Idrees A., Zafar, Ahmad U., Khan, Shaheen N., Husnain, Tayyab, Jiao, Xiaodong, MacDonald, Ian M., Riazuddin, Sheikh, Sieving, Paul A., Katsanis, Nicholas, Hejtmancik, J. Fielding
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blindness; Chromosomes; Chromosomes, Human, Pair 15 - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; General aspects. Genetic counseling; Genes, Recessive; Genetic recombination; Genetics of eukaryotes. Biological and molecular evolution; Humans; Immunohistochemistry; In Situ Hybridization; Medical genetics; Medical sciences; Mice; Molecular and cellular biology; Molecular Sequence Data; Mutation; Night Blindness - genetics; Ophthalmology; Pathogenesis; Proteins; Retina - metabolism; Sequence Analysis, DNA; Sequence Deletion - genetics; Sodium-Calcium Exchanger - genetics; Sodium-Calcium Exchanger - metabolism; Vision disorders
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2010.08.013

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.