ABCA4基因相关的遗传性视网膜变性疾病的表型与基因型分析  

Clinical and genetic analysis of ABCA4 gene-associated hereditary retinal dystrophy

作　　者：梁庆玲[1] 刘勇[1] 孟晓红[1] 阴正勤[1] 

机构地区：[1]第三军医大学西南医院眼科,重庆400038

出　　处：《第三军医大学学报》2016年第8期874-880,共7页Journal of Third Military Medical University

摘　　要：目的在一组ABCA4基因相关的遗传性视网膜变性疾病(hereditary retinal dystrophies,HRD)的无关系先证者中,研究基因型与表型的关系。方法从2013年1月至2015年7月到第三军医大学西南医院眼科就诊的病例中,选出确诊为ABCA4基因突变的6例无关系先证者,应用眼科裂隙灯检查、视力检查、眼底彩色照相、眼底荧光造影、光学相干断层扫描、电生理检查的方法来分析其表型和基因型的关系。结果 6例无关系的先证者中,3例诊断为Stargardt病(Stargardt disease,STGD),2例诊断为视网膜色素变性(视杆-视锥型,retinitis pigmentosa,RP),1例诊断为视锥细胞营养不良(cone dystrophy,COD)。其中,先证者2、6为ABCA4基因的纯合突变,先证者1、3、4、5为ABCA4基因的杂合突变。所有先证者的黄斑中心凹厚度有不同程度变薄,闪光视网膜电图及多焦视网膜电图的各波形也有不同程度的幅值下降及峰时延迟,且临床表现为视网膜色素变性(视杆-视锥型)的患者黄斑区变薄的程度、电生理各波幅值下降程度及峰时延迟程度更显著。结论 ABCA4基因突变可以产生多种临床表型,且同一基因突变方式、同一临床诊断的不同个体病情严重程度有所差异。Objective To investigate the relationship between genotypes and phenotypes in hereditary retinal dystrophy（ HRD） associated with adenosine triphosphate-binding cassette,subfamily A,member 4（ ABCA4） gene mutation. Methods Six irrelevant probands with ABCA4 gene mutation,who were diagnosed in our hospital from January 2013 to July 2015,were included in this study. The correlation between the genotypes and phenotypes was investigated based on the genetic testing results and ophthalmic examinations including silt lamp examination,visual acuity testing,fundus photography,fundus fluorescein angiography（ FFA）,optical coherence tomography（ OCT）,full-field electroretinography（ FERG）,and multifocal electroretinography（ mf ERG）. Results Three irrelevant probands were diagnosed with Stargardt disease,2 with autosomal recessive retinitis pigmentosa（ rod-cone dystrophy） and 1 with cone dystrophy.Mutation of probands 2 and 6 was homozygote,and that of probands 1,3,4 and 5 was heterozygote. The foveal thickness was reduced in all the specimens,and it showed varying modification in different individuals.In addition,FERG and mf ERG showed reduced amplitude and prolonged implicit time in all the probands.These symptoms were especially serious in the probands diagnosed with retinitis pigmentosa. Conclusion ABCA4 gene mutation can produce different clinical phenotypes. The symptom severity of different individuals is variant even if the probands have the same mutation mode or the same clinical diagnosis.

关 键 词：ABCA4 STARGARDT病 视网膜色素变性 视锥细胞营养不良 遗传性视网膜变性疾病 表型 基因型 

分 类 号：R596.2[医药卫生—内科学] R770.43[医药卫生—临床医学]