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- PMID: 19853238
- UKPMCID: 19853238
- DOI: 10.1016/j.ajhg.2009.09.015
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Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa.
Davidson, Alice E; Millar, Ian D; Urquhart, Jill E; Burgess-Mullan, Rosemary; Shweikh, Yusrah; Parry, Neil; O'Sullivan, James; Maher, Geoffrey J; McKibbin, Martin; Downes, Susan M; Lotery, Andrew J; Jacobson, Samuel G; Brown, Peter D; Black, Graeme C M; Manson, Forbes D C
Am J Hum Genet. 2009;85(5):581-92.
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Full-text held externally
- PMID: 19853238
- UKPMCID: 19853238
- DOI: 10.1016/j.ajhg.2009.09.015
Abstract
Bestrophin-1 is preferentially expressed at the basolateral membrane of the retinal pigmented epithelium (RPE) of the retina. Mutations in the BEST1 gene cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant vitreochoroidopathy, and autosomal-recessive bestrophinopathy. Here, we describe four missense mutations in bestrophin-1, three that we believe are previously unreported, in patients diagnosed with autosomal-dominant and -recessive forms of retinitis pigmentosa (RP). The physiological function of bestrophin-1 remains poorly understood although its heterologous expression induces a Cl--specific current. We tested the effect of RP-causing variants on Cl- channel activity and cellular localization of bestrophin-1. Two (p.L140V and p.I205T) produced significantly decreased chloride-selective whole-cell currents in comparison to those of wild-type protein. In a model system of a polarized epithelium, two of three mutations (p.L140V and p.D228N) caused mislocalization of bestrophin-1 from the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are increasingly recognized as an important cause of inherited retinal dystrophy.