Autosomal recessive bestrophinopathy associated with angle-closure glaucoma

Crowley, Claire; Paterson, Rachel L; Lamey, Tina M.; McLaren, Terri L.; Roach, John N. De; Chelva, Enid; Khan, Jane C.

doi:10.1007/s10633-014-9444-z

Cited by 34 publications

(27 citation statements)

References 31 publications

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“…Angle-closed glaucoma was observed in 31% (6/20) of the ARB probands, which is lower than the rate (approximately 50%) found in the Caucasian ARB patients. 5,21,35 A recent Japanese study found no ACG in nine patients from seven unrelated families. 31 Currently, only one study has reported four patients with a homozygous mutation p.C251Y in a Chinese family affected with ACG.…”

Section: Discussionmentioning

confidence: 99%

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Tian

Sun

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Mutations in the BEST1 gene can cause Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The aim of the current study was to establish the BEST1 mutation spectrum in Chinese patients with BVMD and ARB and to describe the phenotypic characteristics of patients carrying BEST1 mutations. METHODS.A total of 37 probands with a clinical diagnosis of BVMD (17 patients) or ARB (20 patients) were recruited for genetic analysis; of these, only 5 probands had a family history. All probands underwent detailed ophthalmic examinations. All coding exons and exon-intron boundaries of the BEST1 gene were screened by PCR-based DNA sequencing. In silico programs were used to analyze the pathogenicity of all the variants. Genomic DNA rearrangements of the BEST1 gene were identified by real-time quantitative PCR (RQ-PCR).RESULTS. For patients with BVMD, single heterozygous BEST1 mutations were identified in 13 patients and compound heterozygous mutations were found in 3 patients. For patients with ARB, biallelic mutations were found in 13 probands and single mutant alleles in six patients. Overall, 36 disease-causing variants (20 novel mutations) of the BEST1 gene were identified, including 28 (77.8%) missense, 3 (8.3%) nonsense, 4 (11.1%) splicing effect, and 1 (2.8%) frameshift small duplication mutations.CONCLUSIONS. The mutation spectrum of the BEST1 gene in Chinese patients differed from those of Caucasian patients. Mutations that cause ARB differ from those that cause BVMD. BEST1 screening is important for precise diagnosis of BVMD or ARB.

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Section: Discussionmentioning

confidence: 99%

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Tian

Sun

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…[21, 22] Bestrophinopathies caused by BEST1 gene mutations are found to be associated with reduced AL, hyperopia and a high incidence of ACG. [6, 8, 9, 23, 24] Up to 50% of ARB patients are at risk of angle closure glaucoma developing as a result of narrow anterior chamber angles. [6, 14] But the role of bestrophin-1 in the development of ACG has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…[26] Therefore we suspect that the fundal changes of these patients may play a role in the development of postoperative refractory flat anterior chamber. The pre-existed extensive subretinal and intraretinal fluid accumulations, caused by impairment of normal fluid homeostasis by the RPE due to bestrophin-1 dysfunction, [6, 23, 27, 28] may raise pressure difference between the posterior chamber/vitreous cavity and the anterior chamber, especially when filtering exists. This might easily cause forward lens movement and refractory shallow anterior chamber after trabeculectomy.…”

Section: Discussionmentioning

confidence: 99%

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Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series

et al. 2017

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PurposeTrabeculectomy has been regarded as a mainstay of initial treatment in eyes of angle closure glaucoma (ACG) with peripheral anterior synechia > 180° in the Chinese population while its efficacy in secondary ACG with BEST1 gene mutation remains unclear. We set out to investigate the treatment outcome of trabeculectomy for secondary ACG in a group of patients with autosomal recessive bestrophinopathy (ARB).MethodsIn this retrospective case series study, 8 secondary ACG patients with ARB and their 4 recruited family members underwent a thorough ophthalmic examination including best-corrected visual acuity, Goldmann applanation tonometry, gonioscopy, and fundus examinations. Ultrasound biomicroscopy, optical coherence tomography (OCT), ultrasound A-scan, B-scan, electro-oculography (EOG), Humphrey perimetry, fundus photography, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were also performed. Blood samples were obtained in the patients and their available family members to analyze the variants of the BEST1 gene. Trabeculectomy was performed in the 8 patients (15 eyes).ResultsThe age of onset varied from 13 to 38 years. The average axial length (AL) of the affected eyes was 21.82 ± 0.92 mm and the average anterior chamber depth (ACD) was 2.19 ± 0.29 mm. There was marked axial shallowing of the anterior chamber in all 15 eyes after trabeculectomy, and was not improved with potent mydriatics. The IOP was elevated in 3 eyes. Variable degree of yellowish subretinal deposits was observed in the posterior retina. The FFA showed punctuate or patched hyperfluorescence suggesting retinal pigment epithelium impairment. The ICGA demonstrated dilatation of choroidal vessels. The OCT revealed diffused neuroretinal detachment in the posterior and midperipheral retina, with intraretinal fluid collections, and hyperreflective subretinal accumulations. The average subfoveal choroidal thickness of the patients was 382.36 ± 80.09 μm. All the patients and enrolled family members carried mutation in BEST1 gene.ConclusionsARB is a rare condition with fundus manifestations mimicking various diseases. Careful discrimination should be taken to exclude any secondary causes for ACG before treatment. Concerning the high incidence of postoperative shallow anterior chamber, selection of filtering surgery should be very careful in these patients.

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“…[8][9][10][11][12][13][24][25][26][27][28][29] An important clinical component of ARB is its autosomal recessive nature with a BEST1-null phenotype, which makes it a potentially attractive candidate for gene replacement therapy. 12 Unlike ARB, most other diseases ascribed to BEST1 mutations are autosomal dominantly inherited.…”

Section: Discussionmentioning

confidence: 99%

A NovelBEST1Mutation in Autosomal Recessive Bestrophinopathy

Lee

Jun

Choi

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee CS, Jun I, Choi S, et al. A novel BEST1 mutation in autosomal recessive bestrophinopathy. Invest Ophthalmol Vis Sci. 2015;56:8141-8150. DOI:10.1167/iovs.15-18168 PURPOSE. To describe the clinical characteristics associated with a newly identified mutant of autosomal recessive bestrophinopathy (ARB) and confirm the associated physiological functional defects.METHODS. Two patients with ARB from one family underwent a full ophthalmic examination, including dilated fundus examination, fundus photography, fluorescein angiography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (OCT), electroretinography (ERG), and electrooculography (EOG). Subsequently, genetic analysis for bestrophin-1 (BEST1) mutations was conducted through direct Sanger sequencing. The effect of ARB-associated mutations of BEST1 on the cellular localization was determined by in vitro experiments. Whole-cell patch clamping was conducted to measure the chloride conductance of wild-type BEST1 and the identified BEST1 mutants in transfected HEK293T cells. RESULTS.Two related patients (66-year-old brother and 52-year-old sister) presented with reduced visual acuity and bilateral symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole. Spectral-domain OCT showed macular thinning with submacular fluid. The female patient had a concomitant macular edema associated with branched retinal vein occlusion in the left eye, which responded well to intravitreal bevacizumab injections. Genetic analysis demonstrated that both patients were compound heterozygous for one novel (Leu40Pro) and one previously identified (Ala195Val) BEST1 variant. HEK293T cells transfected with the identified BEST1 mutant showed significantly small currents compared to those transfected with the wild-type gene, whereas cells cotransfected with mutant and wild-type BEST1 showed good chloride conductance. Cellular localization of BEST1 was well conserved to the plasma membrane in the mutants.CONCLUSIONS. We have identified and described the phenotype and in vitro functional aspects of a new BEST1 mutation causing ARB. Clinically suspected ARB cases warrant genetic confirmation to confirm the diagnosis.

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Autosomal recessive bestrophinopathy associated with angle-closure glaucoma

Cited by 34 publications

References 31 publications

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy

Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series

A NovelBEST1Mutation in Autosomal Recessive Bestrophinopathy

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