Clinical and Genetic Misdiagnosis of Autosomal Recessive Bestrophinopathy

Fung, Adrian T.; Yzer, Suzanne; Allikmets, Rando

doi:10.1001/jamaophthalmol.2013.5363

Cited by 5 publications

(3 citation statements)

References 4 publications

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“…Retinoschisis associated with ARB was previously reported. 5 In our case, ARB was associated with retinoschisis in the right eye. Macular hole was previously reported as a complication to retinoschisis 6 or best vitelliform macular dystrophy 7 ; however, it was not reported before with ARB.…”

Section: Discussionsupporting

confidence: 48%

Macular Hole–related Retinal Detachment Complicating Autosomal Recessive Bestrophinopathy: Clinical Features, Multimodal Imaging, and Surgical Outcome

Abdullatif¹

2023

RETINAL Cases &Amp; Brief Reports

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Purpose: To report a case of full-thickness macular-hole related retinal detachment in a patient with autosomal recessive bestrophinopathy.Methods: A 3-year-old boy presented for squint assessment. In the examination, there were typical features of autosomal recessive bestrophinopathy in the left eye and a macular hole-related retinal detachment in his right eye. Color fundus photography, autofluorescence, fundus fluorescence angiography, and spectral-domain optical coherence tomography were recorded.Results: Optical coherence tomography of the right eye showed a full-thickness macular hole retinal detachment. The retina showed retinoschisis affecting the inner and outer nuclear layer at the fovea and parafoveal region. Also, hyperreflective dots were seen at the hole and on the inner retinal surface. The left eye showed subretinal fluid with stalactite-like extensions into the subretinal space, and hyperreflective material seen above the retinal pigment epithelium. Fundus autofluorescence showed hyperautofluorescence at the fovea of the right eye and punctate hyperautofluorescent spots in the midperiphery of the left eye. After pars plana vitrectomy and temporal internal limiting membrane flap, the hole was closed and all the schitic cavities collapsed at the sixthweek follow-up visit.Conclusion: A full-thickness macular hole-related retinal detachment can develop in autosomal recessive bestrophinopathy in the pediatric age group. Pars plana vitrectomy with temporal internal limiting membrane flap may be helpful for successful surgical repair.

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Section: Discussionsupporting

confidence: 48%

Macular Hole–related Retinal Detachment Complicating Autosomal Recessive Bestrophinopathy: Clinical Features, Multimodal Imaging, and Surgical Outcome

Abdullatif¹

2023

RETINAL Cases &Amp; Brief Reports

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“…We believe that ARB may not be as rare a disease as previously thought and is possibly easily misdiagnosed as other conditions such as chronic central serous chorioretinopathy, fundus flavimaculatus, Vogt-Koyanagi-Harada disease, and other types of vitelliform dystrophies. 13,30 With a high clinical index of suspicion, more cases with new mutations should be identified and reported.…”

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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“…Of course, there are very few patients who do not have a positive family history, just like the two patients in our study, for example, i: parents as heterozygous carriers of the mutated gene, even if it is not a mutation at the same site, it will lead to the diseases of offspring due to the inactivation of biallelic genes; ii: the occurrence of a de novo chromosomal rearrangement, resulting in the appearance of homozygous patients in offspring. When these happen, patients can easily be missed diagnosed or misdiagnosed, we need to consider the various conditions of patients, include clinical manifestations, biochemical examination, and especially genetic defects [18]. Genetic testing technologies, such as NGS, Sanger sequencing and CNVplex technique to detect mutation and copy number of the VWF gene can help patients make a correct diagnosis [19,20].…”

Section: Discussionmentioning

confidence: 99%

Compound heterozygosity for novel von Willebrand factor genetic variants associated with von Willebrand disease in two Chinese patients

Wang¹,

Wang

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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Background Von Willebrand factor (VWF) encodes a secreted glycoprotein involved in primary hemostasis. Genetic mutations in this gene leading to either quantitation or qualitative defects of VWF, result in von Willebrand disease (VWD), an inherited bleeding disorder. Methods In this study, two families with VWD were recruited and submitted to a series of clinical and genetic examinations. prothrombin time, activated partial thromboplastin time, thrombin time, factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo) tests were measured in peripheral blood. F8, F9, and VWF genes were sequenced using next-generation sequencing, and Sanger sequencing was used as a validation method. Results Both families had a child suffered spontaneous bleeding. Patient 1 showed normal VWF:Ag, severely decreased FVIII:C and VWF:RCo. Patient 2 showed severely decreased FVIII:C, VWF:Ag, and VWF:RCo. Compound heterozygous mutations of VWF gene were identified in both patients. Patient 1 had a novel deletion variant c.1910_1932del (p.Gly637AlafsTer5) and a missense variant c.605G>A (p.Arg202Gln). Patient 2 had a novel missense variant c.4817T>A (p.Met1606Lys) and a novel missense variant c.5983C>T (p.Pro1995Ser). Conclusions We described clinical and molecular features of VWD caused by compound heterozygous mutations in two Chinese patients. Our results expand the variation spectrum of the VWF gene and deepen the understanding of the relationship between the genotype and clinical characteristics of VWD.

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Clinical and Genetic Misdiagnosis of Autosomal Recessive Bestrophinopathy

Cited by 5 publications

References 4 publications

Macular Hole–related Retinal Detachment Complicating Autosomal Recessive Bestrophinopathy: Clinical Features, Multimodal Imaging, and Surgical Outcome

Macular Hole–related Retinal Detachment Complicating Autosomal Recessive Bestrophinopathy: Clinical Features, Multimodal Imaging, and Surgical Outcome

A NovelBEST1Mutation in Autosomal Recessive Bestrophinopathy

Compound heterozygosity for novel von Willebrand factor genetic variants associated with von Willebrand disease in two Chinese patients

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