Autosomal Recessive Bestrophinopathy Differential Diagnosis and Treatment Options
Autosomal Recessive Bestrophinopathy Differential Diagnosis and Treatment Options
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DOI：
10.1016/j.ophtha.2012.09.057
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发表时间：
2013-04-01
期刊：
影响因子：
13.7
通讯作者：
van Schooneveld, Mary J.
中科院分区：
文献类型：
--
作者：
Boon, Camiel J. F.;van den Born, L. Ingeborgh;van Schooneveld, Mary J.
目的：描述常染色体隐性遗传性雌激素病（ARB）患者的临床和遗传特征。设计：回顾性病例系列研究。参与者：10例ARB患者来自7个不同的家庭。方法：所有患者进行了完整的眼科检查，包括散瞳眼底检查，眼底照相，荧光素血管造影（FA）。在所有先证者中，进行眼底自发荧光（FAF）成像、光谱域光学相干断层扫描（OCT）、全视野视网膜电图（ERG）、眼电图（EOG）和Goldmann视野检查。在选定的患者中，进行多焦ERG。获得血液样本，以分析BEST 1基因的双等位基因突变，证实了ARB.Main结局指标的诊断：发病年龄;视力;眼底外观; FA，FAF，OCT，全视野ERG和EOG的特征; BEST 1基因突变;和基因型-表型correlation.Results：发病年龄变化很大，从2到54岁。观察到一系列眼底异常，如多灶性淡黄色视网膜下沉积物、视网膜下纤维瘢痕和黄斑囊样视网膜内积液。所有ARB患者均为远视，部分患者前房角较浅，易患闭角型青光眼。所有患者的EOG结果均异常。8例ARB患者的全视野ERG结果异常，而2例患者在全视野ERG上表现出正常的视锥和视杆反应。9例ARB患者在BEST 1基因中携带双等位基因突变，在1例具有特征性ARB表型的患者中，仅可鉴定出1种突变。共检测到7种不同的突变，其中4种为新突变。结论：常染色体隐性遗传性雌激素样肽病是由BEST 1基因的常染色体隐性遗传性突变引起的一种可识别的表型。与其他疾病的鉴别诊断可以根据显著的自体荧光变化结合EOG上的不存在光上升来进行，其超过了全场ERG异常，这表明该疾病的BEST 1相关遗传性质。一些目前可用的治疗方案应考虑在ARB，一种疾病，似乎是一个合适的候选人，为未来的基因therapy.Financial披露（S）：作者（S）没有专有或商业利益，在本文中讨论的任何材料。Ophthalmology 2013;120：809-820（C）2013，美国眼科学会。
Objective: To describe the clinical and genetic characteristics of patients with autosomal recessive bestrophinopathy (ARB).Design: Retrospective case series.Participants: Ten patients with ARB from 7 different families.Methods: All patients underwent a complete ophthalmic examination, including dilated fundus examination, fundus photography, and fluorescein angiography (FA). In all probands, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (OCT), full-field electroretinography (ERG), electro-oculography (EOG), and Goldmann perimetry were performed. In selected patients, multifocal ERG was performed. Blood samples were obtained to analyze the BEST1 gene for biallelic mutations that confirmed the diagnosis of ARB.Main Outcome Measures: Age at onset; visual acuity; fundus appearance; characteristics on FA, FAF, OCT, full-field ERG, and EOG; BEST1 gene mutations; and genotype-phenotype correlation.Results: The age at onset varied widely, from 2 to 54 years. A spectrum of fundus abnormalities was observed, such as multifocal yellowish subretinal deposits, subretinal fibrous scars, and cystoid intraretinal fluid collections in the macula. All ARB patients were hyperopic, and some had shallow anterior chamber angles that predisposed them to angle-closure glaucoma. The EOG results were abnormal in all patients. The full-field ERG results were abnormal in 8 ARB patients, whereas 2 patients demonstrated normal cone and rod responses on full-field ERG. Nine ARB patients carried biallelic mutations in the BEST1 gene, and in 1 patient with a characteristic ARB phenotype, only 1 mutation could be identified. Seven different mutations were detected, including 4 novel mutations.Conclusions: Autosomal recessive bestrophinopathy is a recognizable phenotype caused by autosomal recessively inherited mutations in the BEST1 gene. A differential diagnosis with other conditions can be made on the basis of marked autofluorescence changes in combination with an absent light rise on the EOG that outweighs the full-field ERG abnormalities, which point to the BEST1-related hereditary nature of the disease. A number of currently available therapeutic options should be considered in ARB, a disease that seems to be a suitable candidate for future gene therapy.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:809-820 (C) 2013 by the American Academy of Ophthalmology.