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Purpose: To describe the genotype and phenotype of patients with autosomal recessive bestrophinopathy (ARB), and heterozygous carriers. Methods: The members of three unrelated ARB families were investigated. Molecular genetic analysis was performed on 11 members of these families. Ten members were examined clinically; including visual acuity, slit-lamp examination, biomicroscopy, fundus photography, and Goldmann applanation tonometry. Measurements were also made of the anterior chamber depth and axial length, and optical coherence tomography (OCT), electrooculography (EOG), and full-field electroretinography (full-field ERG) were performed. Multifocal electroretinography (mfERG) was performed on eight members of these families. Results: Two novel combinations of missense mutations in theBEST1gene 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. All four patients with ARB had clinical and electrophysiological features of ARB. All the heterozygous carriers of the p.R141H mutation were clinically normal, and showed normal OCT, EOG and full-field ERG findings, but had mildly abnormal mfERG results. Only one heterozygous carrier of the p.M325T mutation was studied and he was clinically normal, showing normal OCT and full-field ERG results, but subnormal EOG and mfERG findings. The heterozygous carrier of the p.I201T mutation was clinically normal, showing normal OCT, EOG and full-field ERG results, but subnormal mfERG results. Conclusions: We have shown that the two novel combinations of compound heterozygous mutations p.R141H/p.M325T and p.R141H/p.I201T in theBEST1gene can also lead to the ARB phenotype. [ABSTRACT FROM PUBLISHER]

Purpose: To present the clinical and electrophysiological findings in four members of a family with Best vitelliform macular dystrophy (BVMD) and angle-closure glaucoma (ACG)., Methods: Four members of a family with BVMD were examined clinically, including visual acuity, slit-lamp examination, biomicroscopy, Goldmann applanation tonometry and gonioscopy. Measurements of the anterior chamber depth and axial length, visual field, optical coherence tomography, full-field electroretinography, multifocal electroretinography and electrooculography were performed. In addition molecular genetic analysis of the bestrophin-1 gene (BEST1), the microphthalmia-associated transcription factor gene (MITF) and the cone-rod homeobox gene (CRX) were performed., Results: Four family members with the c.253T>C p.Y85H mutation in the BEST1 gene and BVMD in different stages also exhibited anterior segment abnormalities such as shallow anterior chambers (two cases), and reduced axial lengths in all cases. Microphthalmos (axial length ≤ 20mm) was found in the index patient and in her son. Hyperopia was found in all four examined patients. Closed angles/narrow angles were observed in patients with microphthalmos. The index patient developed ACG at the age of 12 years. Her son inherited microphthalmos, severe hyperopia, and narrow angles. He is at risk of developing ACG. No pathogenic mutation of the MITF or the CRX genes was detected in the index patient., Conclusions: BVMD could be associated with anterior segment abnormalities such as shallow anterior chambers, closed/narrow anterior chamber angles and ACG. Ophthalmologists should be aware of the association between ACG and BVMD. Examination of the anterior segment, gonioscopy and intraocular pressure control are recommended in patients with BVMD.

Purpose: To describe morphological and functional changes in a single patient with multifocal Best vitelliform macular dystrophy (BVMD) and to perform a genotype/phenotype correlation., Methods: The proband with multifocal BVMD and three of her family members were examined with electrooculography (EOG), full-field electroretinography (full-field ERG), multifocal electroretinography (mfERG) and optical coherence tomography (OCT). Genomic DNA was screened for mutation in the BEST1 gene by DNA sequencing analysis., Results: The proband was observed regularly during a follow-up period of 4 years. Full-field ERG demonstrated reduced and delayed responses of both rods and cones. OCT demonstrated intra- and subretinal fluid which seemed to fluctuate with periods of stress, similar to that seen in chronic central serous chorioretinopathy. Two distinct heterozygous BEST1 mutations were identified in the proband, the recurrent p.R141H mutation and the p.P233A mutation. Heterozygous p.R141H mutations were also identified in two family members, while p.P233A was a de novo mutation. Abnormal EOG findings were observed in both the proband and in the carriers of p.R141H. Heterozygous carriers showed delayed implicit times in a- and b-waves of combined total rod and cone full-field ERG responses., Conclusions: The p.R141H mutation is frequently seen together with multifocal vitelliform retinopathy and biallelic mutations in BEST1. Our results show that carriers of the p.R141H mutation are clinically unaffected but present with abnormal EOG and full-field ERG findings. A patient with biallelic mutations of the BEST1 gene, causing multifocal BVMD with progressive, widespread functional disturbance of the retina, confirmed by full-field and mfERG is described.