摘要目的 观察多灶性卵黄样视网膜病变(MVR)患者临床特征和BEST1基因筛查结果.方法 回顾性系列病例研究.5个无血缘关系家系的9例MVR患者的18只眼和10名家系中正常成员纳入研究.详细收集患者病史、家族史;患者以及家系正常成员均行最佳矫正视力(BCVA)、眼压、屈光度、裂隙灯显微镜、90D前置镜、前房角镜、眼底彩色照相、频域光相干断层扫描(OCT)、眼底自身荧光(AF)、超声生物显微镜检查以及眼轴长度(AL)测量.行眼电图(EOG)检查12只眼;视野检查13只眼.采集患者及其家系正常成员外周静脉血,提取全基因组DNA.采用聚合酶链反应扩增BEST1基因外显子及其侧翼,Sanger测序检测突变.结果 5个家系中,3例先证者具有家族史,其中1个家系为常染色体显性遗传.测序结果发现BEST1基因突变位点4个.其中,3个错义突变(c.140G＞T,p.R47L;c.232A＞T,p.I78F;c.698C＞T,p.P233L);1个缺失突变(c.910_912del,p.D304del).p.R47L和p.I78F为新发现突变位点.患眼BCVA手动～1.0.平均眼压(30.39±11.86) mmHg(l mmHg=0.133 kPa);平均屈光度(-0.33±1.68)D.闭角型青光眼(ACG) 12只眼,房角关闭(AC)4只眼.EOG光峰/暗谷值＜1.55.平均中央前房深度(2.17±0.29) mm.视野呈旁中心暗点至弥漫性缺损改变.平均AL(21.87±0.63) mm.眼底视网膜后极部呈多灶性卵黄样病变.伴ACG者视盘苍白,杯盘比扩大.频域OCT检查显示视网膜水肿,神经上皮层广泛浅脱离,视网膜下强反射沉积物.AF呈强荧光.黄斑区局灶性脉络膜凹陷1只眼.10名家系正常成员基因检测及临床检查均未见异常.结论 MVR患者携带BEST1基因杂合突变;新发现突变位点p.R47L和p.I78F.眼底呈多灶性卵黄样病变;EOG异常;多数患者伴有AC和(或)ACG.

abstractsObjective To analyze the BEST1 gene mutations and clinical features in patients with multifocal vitelliform retinopathy (MVR).Methods This is a retrospective case series study.Five MVR families with MVR,including 9 patients and 10 healthy family members were recruited.Clinical evaluations were performed in all MVR patients and their family members,including best-corrected visual acuity (BCVA),intraocular pressure (IOP),refraction,slit-lamp examination,90 D preset lens examination,gonioscopy,color fundus photography,optical coherence tomography (OCT),fundus autofluorescence (AF),ultrasound biomicroscopy (UBM) and axial length measurement.Electro-oculogram (EOG) was performed in 12 eyes and visual field were performed in 13 eyes.Peripheral blood samples were collected in all subjects to extract genomic DNA.Coding exons and flanking intronic regions of BEST 1 were amplified by polymerase chain reaction and analyzed by Sanger sequencing.Results Among the 5 MVR families,3 probands from three families had family history,including 1 family had autosomal dominant inheritance pattern.Two patients from 2 families were sporadic cases.Screening of BEST1 gene identified four mutations,including three missense mutations (c.140G＞T,p.R47L;c.232A＞T,p.I78F;c.698C＞T,p.P233L) and 1 deletion mutation (c.910_912del,p.D304del).Two mutations (p.R47L and p.I78F) were novel.The BCVA of affected eyes ranged from hand motion to 1.0.The mean IOP was (30.39± 11.86) mmHg (1 mmHg=0.133 kPa).The mean refractive diopter was (-0.33 ± 1.68) D.Twelve eyes had angle-closure glaucoma (ACG) and 4 eyes had angle closure (AC).EOG Arden ratio was below 1.55 in all patients.The mean anterior chamber depth was (2.17± 0.29) mm.Visual field showed defects varied from paracentral scotoma to diffuse defects.The mean axial length was (21.87± 0.63) mm.All MVR patients had multifocal vitelliform lesions in the posterior poles of retina.ACG eyes demonstrated pale optic disc with increased cup-to-disc ratio.OCT showed retinal edema,extensive serous retinal detachment and subretinal hyper-reflective deposits which had high autofluorescence in AF.The genetic testing and clinical examination were normal in 10 family members.Conclusions MVR patients harbored heterozygous mutation in the BEST1 gene.Two novel mutations (p.R47L and p.I78F) were identified.These patients had clinical features of multifocal vitelliform retinopathy and abnormal EOG.Most patients suffered from AC/ACG.