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Conor Patrick Malone, Matthew Carrigan, Karen Collins, Hilary Dempsey, G Jane Farrar, Paul Kenna; A 1 base-pair frameshift deletion in codon 893 of SLC24A1 causes Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2016;57(12):657.
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© ARVO (1962-2015); The Authors (2016-present)
We report the retinal phenotype associated with a novel mutation in SLC24A1, a gene in which mutations have previously been reported only to cause Congenital Stationary Night Blindness (CSNB), detected in 2 siblings during the course of Target 5000, a next generation sequencing project to genotype Irish patients with inherited retinal degenerations (IRD).
Patients were recruited prospectively and clinically characterized. Assessment included best-corrected visual acuity, Goldmann perimetry, Lanthony D-15 colour vision testing, slit-lamp biomicroscopy, ISCEV clinical standard electroretinography (ERG), colour and autofluorescence fundus photography, and spectral-domain optical coherence tomography. With informed consent, DNA samples drawn from the subjects underwent exon sequencing of 218 retinopathy-associated genes using target-capture oligo panels.
The 52-year-old proband and her 47-year-old sister reported lifelong difficulties seeing in low light. There was no known parental consanguinity. Both retained good central vision until the 5th decade. Goldmann perimetry showed marked concentric constriction in both patients with the IV4e, O4e and I4e targets. ERG revealed non-recordable rod-isolated responses. Cone-isolated responses were normal in timing but significantly reduced in amplitude. Fundoscopy demonstrated bone-spicule intra-retinal pigmentary deposits. A diagnosis of retinitis pigmentosa (RP) was made in each case, with possible autosomal recessive inheritance. Next-generation sequencing revealed that both patients were homozygous for a 1bp frameshift deletion in codon 893 of SLC24A1.
The only retinopathy-associated mutation in SCL24A1, the rod Na-Ca+K exchanger (NCKX) gene, reported to date is a 2bp deletion in exon 2: c.1613_1614del, predicted to cause a frame shift resulting in premature termination of SLC24A1, in a large Pakistani CSNB kindred (Riazuddin et al. 2010). We recently demonstrated that a mutation in GNAT1, mutations in which were previously thought only to result in CSNB, could also cause a late-onset form of RP (Carrigan et al. 2015). Our demonstration of a second pathological mutation in SLC24A1, resulting in an unmistakable form of RP, extends the range of retinal dysfunction which disruption of this gene may cause, and adds to the emerging hypothesis that some forms of CSNB may not be as ‘stationary’ as previously believed.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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