CRB1突变型Leber先天性黑矇和早发视网膜萎缩患儿基因型与表型特征研究  

Genotype and phenotype of CRB1 mutated Leber congenital amaurosis and early-onset retinal atrophy

作　　者：王诗园[1] 张翔[1] 彭婕[1] 胡毅倩[1] 赵培泉[1] Wang Shiyuan;Zhang Xiang;Peng Jie;Hu Yiqian;Zhao Peiquan(Department of Ophthalmology,Xinhua Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院眼科,200092

出　　处：《中华眼底病杂志》2021年第4期284-289,共6页Chinese Journal of Ocular Fundus Diseases

基　　金：国家自然科学基金(81770964)。

摘　　要：目的观察CRB1突变型Leber先天性黑矇(LCA)和早发视网膜萎缩(EOSRD)患儿基因型与表型关系特征。方法回顾性临床研究。2013年1月至2019年12月于上海交通大学医学院附属新华医院眼科临床及基因诊断的CRB1突变LCA和EOSRD患儿10例纳入研究。二代测序及致病性分析为CRB1基因突变,并经一代验证及家系共分离分析予以明确鉴定为CRB1突变型。患儿均行视网膜电图(ERG)、眼底检查。同时行光相干断层扫描(OCT)检查6例,荧光素眼底血管造影(FFA)检查1例,广角激光扫描检眼镜(UWF SLO)检查7例。结果10例患儿中,LCA 6例,EOSRD 4例。首次就诊平均年龄3.61岁。ERG明暗适应波形平坦6例,重度下降4例。成功检测到致病性突变位点19个,其中新发现突变位点9个。纯合突变1例,复合杂合突变9例。眼底视网膜呈"铜钱"样、"椒盐"样、"骨细胞"样色素改变分别为4、2、1例,"结晶"样色素改变1例,黄斑区色素瘢痕2例。行UWF SLO检查的7例,眼底中周部均可见不同程度小动脉旁色素上皮保留(PPRPE)。行OCT检查的6例,视网膜外层萎缩,椭圆体带消失。双眼对称性黄斑囊样水肿、黄斑区劈裂样囊变以及右眼黄斑前膜与视盘及黄斑区粘连各1例;视网膜结构粗糙增厚,中心凹变薄3例。FFA检查,晚期视盘荧光素染色,黄斑区荧光素积聚,各象限沿血管走形呈弥漫性强荧光,周边PPRPE呈"霜枝"样强荧光,呈类葡萄膜炎样改变1例。结论CRB1突变型患者基因型和表型关系复杂,PPRPE是其特征性共性改变。Objective To investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis(LCA)and early onset retinal dystrophy(EOSRD).Methods A retrospective clinical study.From January 2013 to December 2019,10 children with CRB1 mutated LCA/EOSRD were enrolled in the study.The patients were identified as CRB1 mutation by the second generation targeted capture sequencing,Sanger sequencing and the family segregation analysis.All children underwent electroretinogram(ERG)and fundus examination.At the same time,6 cases were examined by optical coherence tomography(OCT);1 case was examined by fluorescein fundus angiography(FFA),7 cases were examined by wide-angle laser scanning ophthalmoscope(UWF SLO).Results There were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations.The average age of first visit was 3.61 years old.The light and dark wave of ERG was flat in 6 cases,and decreased in 4 cases.A total of 19 pathogenic mutations were detected.There were 1 homozygous mutation and 9 compound heterozygous mutations.There were 4,2 and 1 cases of"copper-coin"like,"salt and pepper"like and"osteocyte"like pigment changes in retina,1 case of"crystalline pigment"change and 2 cases of macular pigment scar.In 7 cases of UWF SLO examination,different degrees of para-arteriolar pigment epithelium retention(PPRPE)were found in the middle and peripheral fundus.In 6 cases examined by OCT,the outer layer of retina atrophied and the band of ellipsoid disappeared.Symmetrical cystoid macular edema,splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case,respectively,the retinal structure was rough and thickened,and the fovea became thinner in 3 cases.In FFA examination,1 case showed uveitis-like changes with late optic disc fluorescein staining,macular fluorescence accumulation,strong fluorescence diffusing along the blood vessels in each quadrant,peripheral PPRPE of"frost-branch"like strong fluorescence

关 键 词：Leber先天性黑朦 早发视网膜萎缩 CRB1突变 

分 类 号：R774.1[医药卫生—眼科]