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Anshuman Verma, Thong Nguyen, Poornachandra B, Somasekar Seshagiri, Andrew Peterson, Sameer Phalke, Anuprita Ghosh, Arkasubhra Ghosh; Identification of novel BEST1 mutations in Bestrophinopathy families.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):582.
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© ARVO (1962-2015); The Authors (2016-present)
The BEST1 gene encodes for the Bestrophin protein, a chloride channel required for normal visual functions of the retina. Mutations in BEST 1 have been reported in a few related genetic ocular diseases, autosomal recessive bestrophinopathy (ARB) or Best vitelliform macular dystrophy (BVMD). However, novel mutations associated with new phenotypic variations and the inheritance patterns are still being discovered. In this study, we analyzed four Indian families using whole-exome sequencing and identified unreported BEST1 mutations with their phenotype.
This study was performed with the approval of the Narayana Nethralaya ethics committee and written informed consent of the patients. The subjects underwent ophthalmic examination including fundus imaging, slit lamp examination, fundus autoflourescence and electrophysiology. A total 8 patients with ARB (6 males, 2 females) (age range 11-26 years) and 12 related unaffected members from four unrelated southern Indian families were clinically investigated. Whole exome sequencing was performed for all 20 members using DNA isolated from peripheral blood and data was processed using a DNA sequencing workflow.
The data from 20 samples from the four families in our study resulted in 2,630,722 variants. After filtration, we found BEST1 mutations in all 4 families (hom. p.Y131C in Family A ; hom. p.R150P in Family B ; het.p.R47H and het.p.V216I in Family C; and het.p.T91I in Familly D). The features of families A, B and C suggest ARB while family D is suggestive of BVMD.
The genetic analysis characterized 4 novel BEST1 mutations in four families, two identified with homozygous inheritance and rest two with heterozygous mutations. The presence of compound heterozygous mutations in ARB family C is a novel discovery. In BVMD family D, the heterozygous mutation in asymptomatic parent and the proband suggests the possibility of either incomplete dominance or additional undiscovered genetic features. This report adds to the spectrum of genotypes and phenotypes of BEST1 mutations and will be useful for its accurate clinical and molecular diagnosis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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