常染色体显性遗传视网膜色素变性家系的临床表型和致病突变基因位点鉴定  

IDENTIFICATION OF THE PATHOGENIC MUTATION C.166G>A IN NR2E3 IN AN AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA FAMILY

作　　者：李菁蒴 汤苏珍 刘雅宁 陈鹏[1] LI Jingshuo;TANG Suzhen;LIU Yaning;CHEN Peng(Department of Human Anatomy and Histo-logy and Embryology,Basic Medical College,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院人体解剖与组织胚胎学系

出　　处：《青岛大学学报（医学版）》2020年第1期30-34,共5页Journal of Qingdao University(Medical Sciences)

基　　金：中国博士后科学基金面上项目(2017M612211);山东省自然科学基金资助项目(ZR2018MH016)

摘　　要：目的分析一个中国北方视网膜色素变性(RP)家系病人的临床表型及致病基因突变,寻找致病基因突变位点,探讨表型与基因型之间的关系。方法收集中国北方地区的一个RP家系的临床资料,共有11例家庭成员参与研究,其中包括5例病人和6例正常成员。完善该家系内所有参与研究成员的眼科检查,提取该家系中全部成员的外周血基因组DNA,选取先证者进行视觉系统相关目标区域全外显子组测序,最终通过家系内共分离验证致病突变,进一步分析该突变与病人表型间的关系。结果临床检查显示该家系内5例病人均符合典型的RP表型,目标区域外显子组测序显示核受体亚科2第E组第3个成员(NR2E3)基因c.166G>A突变,该突变导致了NR2E3基因所编码蛋白第56号氨基酸由甘氨酸变为精氨酸(p.56,G>R);保守性分析显示该突变在各物种中高度保守,生物信息学预测结果表明该突变具有较高的致病性。结论该家系内符合典型RP表型病人目标区域外显子组测序发现了NR2E3基因上一个已知的突变(c.166G>A,p.56,G>R),该突变在家系内共分离。Objective To analyze the clinical phenotype and pathogenic gene mutation of a family with retinitis pigmentosa(RP)in northern China,to find the mutation site of pathogenic gene,and to explore the relationship between phenotype and genotype.Methods The clinical data of an RP family in northern China were collected.A total of 11 family members,including 5 patients and 6 normal members,were enrolled in this study.Each of the participating members went through a complete ophthalmic examination.The peripheral blood genomic DNA of each family member was extracted,and the proband was selected for whole exome sequencing of the target region related to the visual system.Finally,a co-segregation analysis within the family was performed to verify the pathogenic mutation,and the relationship between the mutation and the patients’phenotype was further analyzed.Results Clinical examinations showed that all the 5 patients in the family had the typical RP phenotype.Exome sequencing of the target region revealed a mutation of c.166G>A in the nuclear receptor subfamily 2,group E,member 3(NR2E3)gene,which resulted in the change of the 56th amino acid from glycine to arginine(p.56,G>R).A conservative analysis showed that the mutation was highly conserved in various species,and bioinformatics predictions showed that the mutation was highly pathogenic.Conclusion All the patients in this family had the typical RP phenotype.A known mutation in their NR2E3 gene(c.166G>A,p.56,G>R)was revealed according to the exome sequencing of the target region,and the mutation was co-segregated within the family.

关 键 词：视网膜变性 色素细胞 点突变 高通量核苷酸序列分析 NR2E3基因 

分 类 号：R774.13[医药卫生—眼科] R394[医药卫生—临床医学]