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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. and Manson, Forbes D.C. (2009) Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa The American Journal of Human Genetics, 85, (5), pp. 581-592. (doi:10.1016/j.ajhg.2009.09.015.).

Record type: Article


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.

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Published date: 13 November 2009


Local EPrints ID: 73565
ISSN: 0002-9297
PURE UUID: 6ff50a6d-9f49-4b8f-b56a-eca8351bbc0f

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Date deposited: 09 Mar 2010
Last modified: 18 Jul 2017 23:49

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Author: Alice E. Davidson
Author: Ian D. Millar
Author: Jill E. Urquhart
Author: Rosemary Burgess-Mullan
Author: Yusrah Shweikh
Author: Neil Parry
Author: James O'Sullivan
Author: Geoffrey J. Maher
Author: Martin McKibbin
Author: Susan M. Downes
Author: Samuel G. Jacobson
Author: Peter D. Brown
Author: Graeme C.M. Black
Author: Forbes D.C. Manson

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