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

National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan.
The American Journal of Human Genetics (Impact Factor: 10.93). 10/2010; 87(4):523-31. DOI: 10.1016/j.ajhg.2010.08.013
Source: PubMed


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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Available from: Ian Murdoch MacDonald
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    • "Mutations in RP1 were first shown to cause adRCD [9] [10] [11]; however, since 2005, articles have shed light on its implication in arRCD etiology [12] [13] [14] [15] [16] [17] [18] [19] [20]. RP1 mutations were shown to account for ≈5.5% and ≈1% of adRCD and arRCD cases, respectively [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]. Interestingly, Avila-Fernandez et al. [12] reported that a founder nonsense mutation in the Spanish population p.Ser542 * is responsible for 4.5% of arRCD cases suggesting that RP1 mutations are more prevalent in arRCD than previously thought [12]. "
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    • "In the Riggs type [3], rod adaptation is present, although it is slower, and cone responses are normal. This type may be inherited in an autosomal dominant (AD) or autosomal recessive trait [4-7]. The Schubert-Bornschein type is characterized by a negatively shaped dark-adapted ERG response to a bright flash in which the amplitude of the a-wave is normal but larger than that of the b-wave [8]. "
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    • "SLC5A2 is a sodium-dependent glucose transporter and may be involved in diabetic retinal cell death [48]. Mutations in SLC24A1, a gene encoding the photoreceptor-specific sodium/calcium exchanger, have been linked to autosomal recessive congenital stationary night blindness [49]. "
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