The spectrum of ocular phenotypes caused by mutations in the BEST1 gene.
Bestrophin-1 is an integral membrane protein, encoded by the BEST1 gene, which is located in the basolateral membrane of the retinal pigment epithelium. The bestrophin-1 protein forms a Ca(2+) activated Cl(-) channel and is involved in the regulation of voltage-dependent Ca(2+) channels. In addition, bestrophin-1 appears to play a role in ocular development. Over 120 different human BEST1 mutations have been described to date, associated with a broad range of ocular phenotypes. The purpose of this review is to describe this spectrum of phenotypes, which includes Best vitelliform macular dystrophy and adult-onset foveomacular vitelliform dystrophy, autosomal dominant vitreoretinochoroidopathy, the MRCS (microcornea, rod-cone dystrophy, cataract, posterior staphyloma) syndrome, and autosomal recessive bestrophinopathy. The genotype-phenotype correlations that are observed in association with BEST1 mutations are discussed. In addition, in vitro studies and animal models that clarify the pathophysiological mechanisms are reviewed.
Boon
Camiel J F
CJ
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Klevering
B Jeroen
BJ
Leroy
Bart P
BP
Hoyng
Carel B
CB
Keunen
Jan E E
JE
den Hollander
Anneke I
AI
D000818:Animals; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics*; D005128:Eye Diseases / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009154:Mutation; D009799:Ocular Physiological Phenomena / Q000235:genetics; D010641:Phenotype
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins