Researchers already know that patients with particular variations in their BEST1 protein-coding gene can develop a wide spectrum of ocular disorders; but an Oxford-based research team recently found that these patients exhibit substantial phenotypic variability, even within the same variants—leads to significant clinical variability as well. Their case study of 36 patients from 25 families with disease-causing sequence variations in BEST1 identified 22 variants in BEST1 and three distinct clinical phenotypes: autosomal recessive bestrophinopathy (ARB), best vitelliform macular dystrophy (BVMD) and adult-onset vitelliform macular dystrophy. These conditions are clinically distinct and have recognizable phenotypes, the researchers note in their research paper.
The ARB phenotype group had 18 patients from nine families, all of whom had fundus autofluorescence abnormalities and similar SD-OCT features. The researchers identified a phenotype of a beaten metallic retinal appearance extending from the mid periphery to the far periphery in eight patients. Four patients from one family with ARB were previously reported to have autosomal recessive retinitis pigmentosa but were reclassified as having ARB as part of this study.
The BVMD phenotype group comprised 16 patients from 14 families. Fundus features in the macula were consistent with the stage of BVMD. The third group—adult-onset vitelliform macular dystrophy—had only two patients from two families. Their fundus features included small vitelliform lesions. Where available, electro-oculogram results demonstrated a reduced or absent light rise in all patients with ARB and BVMD.
The findings “suggest that the association of autosomal recessive retinitis pigmentosa with sequence variations in BEST1 should be rereviewed,” the researchers concluded in their paper.
|Shah M, Broadgate S, Shanks M, et al. Association of clinical and genetic heterogeneity with BEST1 sequence variations. JAMA Ophthalmol. April 2, 2020. [Epub ahead of print].