Novel BEST1 variant associated with atypical vitelliform macular dystrophy in two siblings: phenotypic and genetic characterization

INTRODUCTION: We describe the phenotypic characteristics and genetic findings in two siblings with vitelliform macular dystrophy within the spectrum of bestrophinopathies caused by a previously unreported BEST1 variant. METHODS: A 53-year-old woman and her 47-year-old brother with long-standing reduced visual acuity and hyperopia underwent comprehensive ophthalmic examination, including fundus imaging, optical coherence tomography (OCT), fundus autofluorescence (FAF), electrooculography (EOG), and genetic testing. RESULTS: The sister's best-corrected visual acuity (BCVA) was 0.62 and 0.66 logMAR, with +6.00 D and +4.50 D hyperopia. The brother showed more advanced disease, with hand motion vision and 0.74 logMAR BCVA, and +5.00 D and +6.25 D hyperopia. Fundus imaging revealed multiple small vitelliform lesions near the vascular arcades and macular retinal pigment epithelium changes without central deposits. OCT showed outer retinal atrophy and subretinal fluid, more severe in the brother. FAF demonstrated hyperautofluorescent vitelliform material surrounding a hypoautofluorescent macula. EOGs were markedly reduced. Genetic testing identified a novel BEST1 variant, c.911A>T (p.Asp304Val), predicted pathogenic. No family history was reported. DISCUSSION: This novel autosomal recessive BEST1 variant expands the clinical and genetic spectrum of bestrophinopathies.