Abstract
To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.