OPN1LW 基因内含子新的剪切变异相关的X染色体连锁遗传性视杆视锥细胞营养不良  

X linked rod-cone dystrophy associated with a novel splicing variation in the intron of OPN1LW gene

作　　者：吴众 施晓萌 李亚 游雅 裴晗 雷博 Wu Zhong;Shi Xiaomeng;Li Ya;You Ya;Pei Han;Lei Bo Henan(Provincial People's Hospital,Henan Eye Institute,Henan Eye Hospital,People's Hospital of Zhengzhou University,Henan Provincial Key Laboratory of Ophthalmology and Visual Science,Henan Clinical Research Center for Eye Diseases,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院,河南省眼科研究所,河南省立眼科医院,郑州大学人民医院,河南省眼科与视觉科学重点实验室,河南省眼科疾病临床医学研究中心,郑州450003

出　　处：《中华实验眼科杂志》2020年第11期957-961,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(81770949)。

摘　　要：目的位于X染色体上的OPN1LW基因变异通常导致蓝色单色视。OPN1LW基因变异多发生在外显子区域,内含子区域的变异少见。本研究分析OPN1LW基因内含子新的剪切变异相关的X染色体连锁遗传性视杆视锥细胞营养不良合并近视家系的临床表型及基因突变特点。方法采用家系调查研究方法,收集2020年1月9日于河南省人民医院临床诊断为视杆视锥细胞营养不良合并近视1家系3代7名成员。对部分家系成员进行眼科检查,采集受试者静脉血并提取DNA,用河南省眼科疾病临床研究中心自主研发的眼后段疾病靶向捕获基因检测试剂盒PS400和全外显子测序法筛选致病基因。用一代Sanger测序和家系共分离法对筛选的靶基因进行验证,参照美国医学遗传学协会(ACMG)指南和在线工具SIFT、Polyphen2、Mutation Taster对新发现的变异位点进行致病性分析。结果先证者5岁,男,临床表现为双眼视力不佳,红绿色盲和眼球震颤。双眼眼前节检查未见明显异常。眼底可见视盘边界清、色淡,黄斑中心凹反光可见。光相干断层扫描(OCT)示双眼黄斑区部分椭圆体带反射模糊,呈颗粒样。全视野ERG显示,双眼暗视0.01 ERG波形记录不到,暗视、明视3.0 ERG a、b波振幅明显降低。先证者舅舅有相似的临床表型,但症状更严重。广角眼底照相示双眼高度近视眼底改变,周边视网膜萎缩并伴有散发黑色圆点病灶;自发荧光示周边视网膜呈弱荧光,中周部未见明显异常。2种二代测序结果均显示OPN1LW基因内含子1个新的半合子剪切变异c.112+2T>G和SEMA4A基因1个新的杂合变异c.1913A>C(p.Y638S)。OPN1LW基因c.112+2T>G变异进一步导致1号内含子经典的剪切体供体序列改变。根据ACMG指南分析显示,c.112+2T>G致病性评分为PVS1+PM2+PP1,为致病性变异。结论本研究首次报道了与OPN1LW基因变异相关的X染色体连锁遗传性视杆视锥细胞营养不良合并近视Objective Mutations in the OPN1LW gene located in X chromosome usually lead to blue cone monochromacy.Variations in OPN1LW gene usually occur in the exon region,but was rare in the intron region.This study was to report a Chinese family with X-linked rod-cone dystrophy associated with a novel OPN1LW gene hemizygotic splicing variation and analyze the clinical phenotype and gene mutation characteristics Methods A pedigree investigation was performed.The family members clinically diagnosed as rod-cone dystrophy with myopia were enrolled in Henan Provincial People's Hospital on January 9,2020.Detailed ophthalmological examination was carried out,and the periphery venous blood was collected for DNA extraction.The target gene sequencing panel PS400 developed by Henan Clinical Research Center for Eye Diseases and whole exon sequencing were used to detect pathogenic mutations.Sanger sequencing and pedigree co-segregation were used to verify variations.The pathogenicity of the novel variation was analyzed based on American College of Medical Genetics(ACMG)Guidelines and online tools SIFT,Polyphen2,Mutation Taster.This study adhered to the Declaration of Helsinki,and the study protocol was approved by the Medical Ethics Committee of Henan Eye Hospital(HNEECKY-2019[15]).Written informed consent was obtained from each family member before any medical examination.Results The proband was a 5-year-old boy with poor vision,red-green blindness and nystagmus in both eyes.No obvious abnormality in ocular anterior segment was found.The boundary of optic disc was clear and the color was reddish,and the reflection of macular fovea was clearly visible.OCT image showed indistinct reflection of some ellipsoids in macular area of both eyes.The amplitudes of a and b waves of full-field ERG were not recorded in scotopic 0.01 scale and significantly reduced in scotopic 3.0 and photopic 3.0 ERG.The uncle of the proband had a more severe clinical phenotype.Wide-angle fundus photography showed high myopia findings,peripheral retinal atrophy an

关 键 词：视杆视锥细胞营养不良 OPN1LW 内含子变异 视网膜 视网膜电图 

分 类 号：R774.1[医药卫生—眼科]