NEW BEST1 MUTATIONS IN AUTOSOMAL RECESSIVE BESTROPHINOPATHY

BEST1 (VMD2) is a gene located on the long arm of chromosome 11 (11q12.3) that encodes for the 585 amino acid transmembrane protein bestrophin 1, located on the basolateral aspect of retinal pigment epithelial (RPE) cells.1 The exact function of bestrophin 1 is still not unequivocally characterized, but it is linked to transepithelial chloride flow possibly by controlling Ca2+ channels in the RPE.1–3 Mutations in BEST1 therefore affect RPE metabolism, and by consequence outer retinal function with which the RPE is intimately associated. Over 200 mutations in BEST1 have been identified and published.1,3,4 Mutations are associated with Best vitelliform macular dystrophy (VMD, MIM 153700), adult-onset vitelliform macular dystrophy (MIM 608161), retinitis pigmentosa 50 (RP50, MIM 613194), and autosomal dominant vitreoretinochoroidopathy (MIM 193220). These diseases are all caused by autosomal dominant mutations. Recently, a phenotype caused by autosomal recessive mutations in BEST1 was described: autosomal recessive bestrophinopathy (ARB, OMIM 611809). Autosomal recessive bestrophinopathy is a rare ocular disease. It was defined by Burgess et al1 in 2008, although the same condition with compound heterozygous mutations in VMD2 had been described 2 years earlier.5 It results from biallelic mutations in BEST1 and is characterized by a multifocal vitelliform dystrophy with subretinal fluid. An association with hypermetropia and angle closure has been described.1 Herein, we review the clinical features and mutation analysis of four families with ARB.