OCT findings in young asymptomatic subjects carrying familial BEST1 gene mutations

Abstract

Purpose: Best disease is an autosomal dominant retinal degeneration characterized by the presence of yellow lesions in the macula causing decreased central visual acuity at later stages. Best disease is caused by heterozygous mutations in BEST1, a gene located at chromosome 11q13. In the present study, we describe the clinical and molecular analysis of two multigenerational families with Best disease and correlate the optical coherence tomography (OCT) findings in asymptomatic and symptomatic subjects carrying BEST1 mutations.Methods: Two Mexican families with 3 affected generations each were studied. Probands underwent full ophthalmologic examination including fundus examination, fluorescent angiography (FAG), and electro-oculogram (EOG). Fourier-domain 3D OCT was performed in a number of symptomatic and asymptomatic subjects from these two pedigrees. PCR amplification and automated nucleotide sequencing of the 11 exons of the BEST1 gene in genomic DNA were also performed.Results: Eighteen members of family 1 were molecularly tested. Seven subjects, including 4 young asymptomatic patients, carried a W24C heterozygous mutation in BEST1. OCT imaging in a 6-year-old asymptomatic patient carrying this mutation did not demonstrate retinal lesions. Fifteen subjects from family 2 were molecularly tested. Four patients, including 2 asymptomatic subjects, carried a heterozygous Q293K BEST1 mutation. OCT imaging in an asymptomatic 8-year-old individual with the Q293K mutation demonstrated bilateral subfoveal lesions and unilateral serous retinal detachment. Symptomatic patients showed severe retinal lesions by OCT.Conclusions: Our results add to the clinical, imaging, and molecular knowledge of Best disease and suggest that OCT can recognize retinal lesions in some asymptomatic carriers of BEST1 mutations as early as 8 years of age.