精母细胞相关蛋白基因变异致象限性视网膜色素变性伴黄斑营养不良一家系临床表型及基因型分析  

Genotypic and phenotypic analysis in a family affected with sector retinitis pigmentosa and macular dystrophy caused by Spermatogenesis-associated protein 7 gene

作　　者：周玲玲 童妍 严江波 沈吟[1] Zhou Lingling;Tong Yan;Yan Jiangbo;Shen Yin(Eye Center,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院眼科中心,武汉430060

出　　处：《中华眼底病杂志》2022年第8期643-649,共7页Chinese Journal of Ocular Fundus Diseases

基　　金：国家重点研发计划(2017YFE0103400)。

摘　　要：目的观察并分析象限性视网膜色素变性(sector RP)的致病基因及临床表型。方法回顾性临床研究。2021年4月于武汉大学人民医院眼科就诊的sector RP一家系的1例患者(先证者)及其父母纳入研究。详细询问病史并行最佳矫正视力(BCVA)、眼底彩色照相、自身荧光(AF)、视野、光相干断层扫描(OCT)、视网膜电图(ERG)、荧光素眼底血管造影(FFA)、吲哚青绿血管造影(ICGA)检查。采集先证者及其父母的外周静脉血3 ml,提取全基因组DNA。全外显子测序,采用Sanger测序及实时定量聚合酶链反应对变异位点进行验证,并进行生物信息学分析和共分离分析。结果先证者男,17岁。双眼视力渐进性下降2年。双眼BCVA均为0.4;视网膜血管变细,黄斑区营养不良,无明显色素沉着;眼底AF检查,鼻下象限视网膜变性呈斑驳影,黄斑呈"花瓣状"强AF;视野检查,双眼对称性颞上方视野缺失;OCT检查,中心凹区域以外光感受器层消失;ERG检查,暗适应波幅降低、明适应呈熄灭状态;FFA和ICGA检查,视盘周围及下方视网膜色素上皮层萎缩。其父母眼部表型正常。基因检测结果显示,先证者SPATA7基因第10号外显子存在一错义突变c.1112T>C(p.Ile371Thr),导致编码的SPATA7蛋白第371号氨基酸由异亮氨酸变成苏氨酸;其母亲携带c.1112T>C杂合突变。根据美国医学遗传学和基因组学学院(ACMG)遗传变异分类标准与指南,该变异为意义不明确变异。同源染色体存在一来源于父亲的拷贝数变异,导致SPATA7基因第10号外显子缺失。根据ACMG指南,该变异为可能致病变异。结论sector RP可累及黄斑,导致黄斑营养不良;SPATA7基因c.1112T>C(p.Ile371Thr)错义突变可能是本家系的致病原因。Objective To analyze the pathogenic gene and clinical phenotypes of a family affected with rare sector retinitis pigmentosa(sector RP).Methods A retrospective clinical study.A patient with sector RP diagnosed in Renmin Hospital of Wuhan University and his parents were included in the study.Detailed medical history was collected;best corrected visual acuity(BCVA),fundus color photography,autofluorescence(AF),visual field,optical coherence tomography(OCT),electroretinogram,fluorescein fundus angiography(FFA),indocyanine green angiography(ICGA)examination were performed.The peripheral venous blood of the patient and his parents were collected,and DNA was extracted.A whole exon sequencing was used for the proband.The mutations were verified by targeted Sanger sequencing and quantitative polymerase chain reaction.Bioinformatics analysis and cosegregation analysis were performed.Results The proband,a 17-year-old male,had presented with gradually decreased vision in the past 2 years with BCVA of 0.4 in both eyes.Retinal vessels attenuation and macular dystrophy without obvious pigmentation on the fundus were observed.AF showed,in bilateral eyes,a symmetrical hypo-autofluorescent region only in the inferonasal quadrant and"petal-like"hyper-AF macula.The visual field examination showed defects in the superotemporal quadrant corresponding to the affected retina.OCT showed loss of the photoreceptor layer except for the foveal region.Electroretinogram examination presented reduced scotopic wave peaks and extinct photopic response.FFA and ICGA showed the atrophy retinal pigment epithelium around the optic disk and in the inferior retina.The clinical phenotypes of the parents were normal.The whole exon sequencing identified one mutation in SPATA7 gene,c.1112T>C(p.Ile371Thr)in exon10 and a copy number variation in trans.The missense mutation resulted in the change of isoleucine to threonine at amino acid 371 in the encoded SPATA7 protein,and the mother carried this heterozygous mutation c.1112T>C.According to the guidelines of

关 键 词：色素性视网膜炎 黄斑营养不良 基因 突变 SPATA7基因 

分 类 号：R774[医药卫生—眼科]