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. American Journal of Human Genetics, 85, (5), 581-592. (doi:10.1016/j.ajhg.2009.09.015.).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.ajhg.2009.09.015.
Related URLs:
Subjects: R Medicine > RE Ophthalmology
Divisions : University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
ePrint ID: 73565
Accepted Date and Publication Date:
13 November 2009Published
Date Deposited: 09 Mar 2010
Last Modified: 31 Mar 2016 13:06
URI: http://eprints.soton.ac.uk/id/eprint/73565

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