New phenotypic and genotypic findings in autosomal recessive bestrophinopathy

Purpose: To report the ocular phenotype in autosomal recessive Bestrophinopathy (ARB) patients and carriers, and to describe novel BEST1 mutations.

Methods: Patients with clinically suspected and subsequently genetically proven ARB underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral-domain optical coherence tomography, electroretinography and electro-oculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing.

Results: Five affected patients from four families were identified. Mean age was 16 years (range, 6 years to 42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent, subretinal, yellowish deposits within the posterior pole. Spectral-domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In one patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected.

Conclusion: In childhood patients with ARB have a recognizable phenotype including multifocal vitelliform subretinal lesions with subfoveal fluid and a cystoid maculopathy. Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing ARB are mostly located outside of the exons that usually harbor VMD-associated dominant mutations.