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Lauren A Dalvin, Jackson Abou Chehade, John (pei wen) Chiang, Josefine Fuchs, Raymond Iezzi, Alan D Marmorstein; Association of a BEST1 Mutation with Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2016;57(12):655.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in BEST1 are associated with 5 clinically distinct diseases, commonly referred to as the bestrophinopathies. The bestrophinopathies include adult onset vitelliform dystrophy (AVMD), Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy (ARB), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and retinitis pigmentosa (RP). Only one study has identified mutations in BEST1 associated with retinitis pigmentosa (RP), and the findings described in that study were atypical of RP with some features of ADVIRC or ARB. Here we report a new subject with RP apparently due to a novel deletion mutation in BEST1.
A 16-year-old male was referred from Denmark with poor visual acuity, visual field loss, and cystoid macular edema. Clinical examination, visual field testing, optical coherence tomography (OCT), OCT angiography (OCTA), electroretinography, and electrooculography were used to confirm the classic RP phenotype. Genetic testing of the proband and both parents was carried out by the University of Oregon, Casey Eye Institute, Molecular Diagnostic Laboratory using a panel of 131 retinal dystrophy genes.
The proband, but not his parents were found to exhibit a classical RP phenotype, which included extensive bone spicules and cystoid macular edema in the presence of generalized visual field constriction, depressed rod and cone electroretinogram (ERG) responses, and reduced Arden ratios on electrooculogram (EOG). A novel heterozygous deletion of 9348 bases (61729891-61733239) from the BEST1 gene resulting in the mutation H422fsX431 was identified in the proband but not in either parent. The deletion begins within exon 10 of the BEST1 gene and extends beyond exon 11 resulting in a frame shift causing deletion of 146aa from Best1, and extending into the adjacent ferritin heavy chain (FTH) gene on the opposite strand of DNA. The proband did not exhibit any symptoms of ferritin deficiency.
BEST1 mutations play a role in some cases of RP. However, it is difficult to understand why some mutations associate with peripheral retinal degeneration phenotypes like RP and ADVIRC, while others manifest as macular degeneration phenotypes. The identification of additional cases of RP associated with a deletion in BEST1 should improve our ability to elucidate the differential pathogenesis of the 5 bestrophinopathies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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