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.
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Camiel J F
CJ
Boon
B Jeroen
BJ
Klevering
Bart P
BP
Leroy
Carel B
CB
Hoyng
Jan E E
JE
Keunen
Anneke I
AI
den Hollander
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