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Abstract：
OBJECTIVE: To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS).
METHODS: Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants.
RESULTS: Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9-68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5.
CONCLUSIONS: This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.
METHODS: Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants.
RESULTS: Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9-68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5.
CONCLUSIONS: This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.
摘要：
目的：通过多模态成像和下一代测序（NGS），为中国常染色体隐性遗传型β-β病（ARB）患者的BEST1突变提供基因型和表型特征。
方法：一项回顾性队列研究包括来自17个不相关的中国血统的ARB家庭的17例患者。表型特征，包括眼前段特征，通过多模态成像进行评估。多基因小组测试，涉及586个眼科疾病相关基因，进行Sanger测序以鉴定致病变异。
结果：在17例ARB患者中，平均随访15.65个月,平均发病年龄30.53岁(范围:9~68岁).最佳矫正视力范围从光感知到0.8。EOG记录显示12例患者的Arden比率通常降低，两名患者的Arden比率正常或略有下降。前特征包括浅前房（16/17），纤毛旋前（16/17），虹膜波贝（13/17），iridoschisis(2/17),虹膜高原（1/17），窄的角度（16/17）和减少的轴向长度（16/17）。16例患者有多个双侧小，圆形,黄色卵黄状沉积物分布在整个后极，围绕着视盘.初步诊断包括闭角型青光眼（4例），最佳疾病（三名患者），和继发于脉络膜新生血管（CNV）的中心性浆液性脉络膜视网膜病变（1例），其余患者被诊断为ARB。十四名患者接受了预防性激光周围虹膜切开术，其中4人还因眼压失控而接受了双眼小梁切除术和虹膜切开术联合治疗.一名患者接受玻璃体内康柏西普治疗CNV。总的来说,确定了15种不同的BEST1致病变体，14例（82.35%）患者发生错义突变。常见的突变包括p。Arg255-256和p。Ala195Val（均为23.68％），外显子7和5中最常见的位点。
结论：这项研究提供了ARB眼前段和遗传特征的综合特征，有各种各样的形态异常.研究结果与完善临床实践和遗传咨询以及推进发病机理研究有关。
方法：一项回顾性队列研究包括来自17个不相关的中国血统的ARB家庭的17例患者。表型特征，包括眼前段特征，通过多模态成像进行评估。多基因小组测试，涉及586个眼科疾病相关基因，进行Sanger测序以鉴定致病变异。
结果：在17例ARB患者中，平均随访15.65个月,平均发病年龄30.53岁(范围:9~68岁).最佳矫正视力范围从光感知到0.8。EOG记录显示12例患者的Arden比率通常降低，两名患者的Arden比率正常或略有下降。前特征包括浅前房（16/17），纤毛旋前（16/17），虹膜波贝（13/17），iridoschisis(2/17),虹膜高原（1/17），窄的角度（16/17）和减少的轴向长度（16/17）。16例患者有多个双侧小，圆形,黄色卵黄状沉积物分布在整个后极，围绕着视盘.初步诊断包括闭角型青光眼（4例），最佳疾病（三名患者），和继发于脉络膜新生血管（CNV）的中心性浆液性脉络膜视网膜病变（1例），其余患者被诊断为ARB。十四名患者接受了预防性激光周围虹膜切开术，其中4人还因眼压失控而接受了双眼小梁切除术和虹膜切开术联合治疗.一名患者接受玻璃体内康柏西普治疗CNV。总的来说,确定了15种不同的BEST1致病变体，14例（82.35%）患者发生错义突变。常见的突变包括p。Arg255-256和p。Ala195Val（均为23.68％），外显子7和5中最常见的位点。
结论：这项研究提供了ARB眼前段和遗传特征的综合特征，有各种各样的形态异常.研究结果与完善临床实践和遗传咨询以及推进发病机理研究有关。
