The Bestrophinopathies

Abstract

AbstractPurpose To describe the phenotypes of conditions due to mutations in BEST1, the gene encoding bestrophin‐1.Methods A case presentation format will be used to illustrate the phenotypes and genotypes of the different bestrophinopathies, with special attention to both the clinical and electrophysiological features that distinguish one phenotype from the other, and those they have in common. In addition, the different BEST1 genotypes will be discussed.Results The phenotypes of Best vitelliform macular dystrophy (BVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and autosomal recessive bestrophinopathy (ARB) are very different as far as their clinical phenotypes are concerned. Nevertheless at the electrophysiological level, they share an abnormal electro‐oculography (EOG) as a common feature. Electroretinography is normal in BVMD, whereas a rod‐cone dystrophy is evident in the later stages of disease of ADVIRC and ARB. The BEST1 genotypes differ in that BVMD is due to a heterozygous missense mutation in BEST1, ADVIRC is due to interaction of several bestrophin protein isoforms, and ARB is probably the null phenotype.Conclusion The phenotypes of the bestrophinopathies are diverse, although they share an abnormal EOG as the common feature. The specific genotypes are also different, leading to different molecular pathogenetic mechanisms.