Novel &lt;b&gt;&lt;i&gt;BEST1&lt;/i&gt;&lt;/b&gt; Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy

Liu, Jingshu; Zhang, Yongjin; Xuan, Yue; Liu, Wei; Wang, Min

doi:10.1159/000444681

Cited by 15 publications

(11 citation statements)

References 22 publications

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“…This phenomenon of phenotypic and allelic heterogeneity highlights a significant phenotypic overlap among BEST1 -linked disorders, posing a challenge in both determining the diagnostic specificity as well as predicting the outcomes of visual impairment. In recent years, the complexity of genotype-phenotype correlation in bestrophinopathies has proven difficult to explain with traditional models of disease pathogenesis (Allikmets et al, 1999; Boon et al, 2007; Yu et al, 2007; Querques et al, 2009; Booij et al, 2010; Liu et al, 2016), indicating a presence of potential genetic modifiers or still undetermined Best1 protein interactors, involvement of environmental components or a combination of both. This likely would point to a complex interplay of genetic susceptibility factors and modifiable environmental stimuli utilizing novel signaling pathways in the retina.…”

Section: Introductionmentioning

confidence: 99%

Bestrophinopathy: An RPE-photoreceptor interface disease

Guziewicz

Sinha

Gómez

et al. 2017

Progress in Retinal and Eye Research

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Bestrophinopathies, one of the most common forms of inherited macular degenerations, are caused by mutations in the BEST1 gene expressed in the retinal pigment epithelium (RPE). Both human and canine BEST1-linked maculopathies are characterized by abnormal accumulation of autofluorescent material within RPE cells and bilateral macular or multifocal lesions; however, the specific mechanism leading to the formation of these lesions remains unclear. We now provide an overview of the current state of knowledge on the molecular pathology of bestrophinopathies, and explore factors promoting formation of RPE-neuroretinal separations, using the first spontaneous animal model of BEST1-associated retinopathies, canine Best (cBest). Here, we characterize the nature of the autofluorescent RPE cell inclusions and report matching spectral signatures of RPE-associated fluorophores between human and canine retinae, indicating an analogous composition of endogenous RPE deposits in Best Vitelliform Macular Dystrophy (BVMD) patients and its canine disease model. This study also exposes a range of biochemical and structural abnormalities at the RPE-photoreceptor interface related to the impaired cone-associated microvillar ensheathment and compromised insoluble interphotoreceptor matrix (IPM), the major pathological culprits responsible for weakening of the RPE-neuroretina interactions, and consequently, formation of vitelliform lesions. These salient alterations detected at the RPE apical domain in cBest as well as in BVMD- and ARB-hiPSC-RPE model systems provide novel insights into the pathological mechanism of BEST1-linked disorders that will allow for development of critical outcome measures guiding therapeutic strategies for bestrophinopathies.

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Section: Introductionmentioning

confidence: 99%

Bestrophinopathy: An RPE-photoreceptor interface disease

Guziewicz

Sinha

Gómez

et al. 2017

Progress in Retinal and Eye Research

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“…For example, retinal lesions in BVMD typically occur bilaterally and symmetrically; however, rarely, patients can exhibit unilateral maculopathy ( 5 , 6 ). Patients with atypical BVMD presentation can have multifocal macular and extramacular involvement, including retinitis pigmentosa, microcornea, retinal dystrophy, cataract, and posterior staphyloma syndrome ( 6 – 13 ). Macular degeneration in BVMD can begin from childhood or adulthood, and is classified as juvenile-onset BVMD or adult-onset BVMD, respectively ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…Macular degeneration in BVMD can begin from childhood or adulthood, and is classified as juvenile-onset BVMD or adult-onset BVMD, respectively ( 14 ). The variation in the age of onset is not clearly understood, and few studies have compared the differences between these two classifications ( 13 , 15 ). Currently, there is no effective treatment for BVMD.…”

Section: Introductionmentioning

confidence: 99%

Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy

Gao

et al. 2017

Mol Med Report

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Best vitelliform macular dystrophy (BVMD) is a hereditary retinal disease characterized by the bilateral accumulation of large egg yolk-like lesions in the sub-retinal and sub-retinal pigment epithelium spaces. Macular degeneration in BVMD can begin in childhood or adulthood. The variation in the age of onset is not clearly understood. The present study characterized the clinical characteristics of two Chinese patients with either juvenile-onset BVMD or adult-onset BVMD and investigated the underlying genetic variations. A 16-year-old male (Patient 1) was diagnosed with juvenile-onset BVMD and a 43-year-old female (Patient 2) was diagnosed with adult-onset BVMD. Comprehensive ophthalmic examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography imaging and Espion electrophysiology. Genomic DNA was extracted from peripheral blood leukocytes collected from these patients, their family members, and 200 unrelated subjects within in the same population. The 11 exons of the bestrophin-1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. Both patients presented lesions in the macular area. In Patient 1, a heterozygous mutation c.903T>G (p.D301E) in exon 8 of the BEST1 gene was identified. This mutation was not present in any of the unaffected family members or the normal controls. Polymorphism phenotyping and the sorting intolerant from tolerant algorithm predicted that the amino acid substitution D301E in bestrophin-1 protein was damaging. In Patient 2, a single nucleotide polymorphism c.1608C>T (p.T536T) in exon 10 of the BEST1 gene was identified. These findings expand the spectrum of BEST1 genetic variation and will be valuable for genetic counseling and the development of therapeutic interventions for patients with BVMD.

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“…Best vitelliform macular dystrophy (BVMD), also known as Best disease, is a dominant, bilateral, symmetric, progressive disease of the macular area; patients present with symptoms of metamorphopsia, blurred vision and a decrease in central vision ( 1 , 2 ). BVMD usually has an early onset, often in the first decade of life ( 3 , 4 ); however, there are some atypical types of BVMD ( 2 ). It is the second most common form of juvenile macular degeneration and accounts for about 1% of all cases of macular degeneration ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Bestrophin 1 gene analysis and associated clinical findings in a Chinese patient with Best vitelliform macular dystrophy

Gao

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate the clinical characteristics and the underlying genetic causes of Best vitelliform macular dystrophy (BVMD) in a sporadic case in a Chinese patient. A 10-year-old boy was diagnosed with BVMD; complete ophthalmic examinations were performed, including best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photograph, optical coherence tomography and fundus fluorescein angiography imaging. Genomic DNA was extracted from leukocytes of the peripheral blood collected from this patient and his family members. DNA samples from 200 unrelated subjects from the Chinese population were used as controls. A total of 11 exons of the bestrophin 1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. The results revealed that the patient presented with yellowish lesions in the macular area. Heterozygous mutations c.292G>A (p.Glu98Lys) in exon 4 and c.1608C>T (p.Thr536Thr) in exon 10 of the BEST1 gene were identified in this sporadic case; however, this was not identified in any of his unaffected family members or in the normal controls. The c.292G>A (p.Glu98Lys) mutation has not been previously reported, whereas the c.1608C>T (p.Thr536Thr) mutation is a previously characterized single nucleotide polymorphism (SNP). In conclusion, BEST1 gene mutations and polymorphisms have been reported in diverse ethnic groups, and the present study identified a novel BEST1 gene mutation and an SNP that occurred simultaneously in a Chinese patient with BVMD.

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Novel <b><i>BEST1</i></b> Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy

Cited by 15 publications

References 22 publications

Bestrophinopathy: An RPE-photoreceptor interface disease

Bestrophinopathy: An RPE-photoreceptor interface disease

Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy

Bestrophin 1 gene analysis and associated clinical findings in a Chinese patient with Best vitelliform macular dystrophy

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