Mutations in the BEST1 gene cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant vitreochoroidopathy, and autosomal-recessive bestrophinopathy.
Mutations in the BEST1 gene cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant vitreochoroidopathy, and autosomal-recessive bestrophinopathy.
Our current and past results indicate that mislocalization of Best1 is not an absolute feature of any individual bestrophinopathy, occurring in AVMD, BVMD, and ARB.
Sanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N-terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C-terminal domain segregating in the BVMD family.
Taken together, our data provide insight into the molecular pathways of dominantly and recessively acting BEST1 missense mutations suggesting that the site of subcellular protein quality control as well as the rate and degree of mutant protein degradation are ultimately responsible for the distinct retinal disease phenotypes in BD and ARB.
The aim of the current study was to establish the BEST1 mutation spectrum in Chinese patients with BVMD and ARB and to describe the phenotypic characteristics of patients carrying BEST1 mutations.
The effect of ARB mutations on the cellular localization of bestrophin-1 was determined by confocal immunofluorescence on transiently transfected MDCK II cells that had been polarized on Transwell filters.
The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1.
To describe the presenting features and functional outcomes in a series of patients with choroidal neovascular membrane complicating BEST1-related retinopathy (Best disease and autosomal recessive bestrophinopathy).
Two novel combinations of missense mutations in the BEST1 gene were identified: p.R141H/p.M325T in three patients with ARB in two unrelated Norwegian families, and p.R141H/p.I201T was found in an ARB patient in a Swedish family.