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Isabelle S Audo, Saddek Mohand-Said, Brigitte Ekpe, Aline Antonio, Christel Condroyer, Fiona Boyard, José Alain sahel, Christina Zeitz; Mutation spectrum of a French cohort with autosomal recessive bestrophynopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1239.
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© ARVO (1962-2015); The Authors (2016-present)
In 2008, Burgess et al. reported a peculiar retinal dystrophy designated as autosomal recessive bestrophinopathy (ARB, MIM #611809) in which atypical retinal abnormalities were associated with an abolished light rise in the Electrooculogram (EOG), a common electrophysiological feature with Best disease (MIM #153700). The phenotype, associated with biallelic BEST1 mutations, is however more severe with variable degrees of full field electroretinogram (ERG) abnormalities, neurosensory retinal detachment, intra retinal cysts and yellowish flecks. The purpose of our study was to genetically characterize a cohort of patients with typical phenotypic feature and attempt a phenotype/genotype correlation.
Patients with a presumed diagnosis of ARB were reviewed. Subjects underwent full ophthalmic examination. Informed consent was obtained from each patient and available family members. The study protocol adhered to the tenets of the Declaration of Helsinki and was approved by the local ethics committee. Sanger sequencing of all 11 exons and flanking region of BEST1 (NM_004183.3) was applied to patients' DNA with a presumed clinical diagnosis of ARB and available family members.
Thirteen patients from 12 families with a diagnosis of ARB were selected in this study. Patient's age at time of examination ranges from 8 to 58 with an average age of 30. Best corrected visual acuity on the ETDRS chart ranges from light perception to 20/25; 55% of the patients were hyperopic and 3 of them had history of closed angle glaucoma; 67% of the patients had generalized retinal dysfunction with a majority affected rod responses more than cone. Regarding genetic screening, 5 of the patients carried compound heterozygous and 7 (2 including siblings) were homozygous for likely disease causing mutations. These variants include 10 missense among which 5 are novel, 3 nonsense with one novel, 2 small deletions which are all novel and one small already reported insertion. One of the novel missense variant (c.91C>A p.Leu31Met) was found at the homozygous status in the two affected siblings and in one unrelated subject, all originating from Morocco which may suggests a founder effect.
Our study identifies novel BEST1 variants underlying ARB. Further 3D modeling and in vitro assays will be needed to better understand functional consequences of these variants to contribute to a better understanding of this disorder.
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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