论文部分内容阅读
目的:观察n 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。n 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n 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n 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n 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。n 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。n “,”Objective:To investigate the relationship between genotype and phenotype in children with n CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD).n Methods:A retrospective clinical study. From January 2013 to December 2019, 10 children with n CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as n 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).n Results:There were 6 cases of LCA and 4 cases of EOSRD in 10 patients with n 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.n Conclusion:The relationship between genotype and phenotype of n CRB1 mutation is complex, and PPRPE is a common characteristic change.n