Morphological and functional changes in multifocal vitelliform retinopathy and biallelic mutations in BEST1

To describe morphological and functional changes in a single patient with multifocal Best vitelliform macular dystrophy (BVMD) and to perform a genotype/phenotype correlation.

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.

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.

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.