先天性无虹膜1家系临床特征及基因检测分析  

Clinical features and gene detection analysis in a family with congenital aniridia

作　　者：李伟候 刘丹宁[1] LI Weihou;LIU Danning(Department of Ophthalmology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing,400010,China)

机构地区：[1]重庆医科大学附属第二医院眼科,重庆400010

出　　处：《陆军军医大学学报》2024年第11期1277-1283,共7页Journal of Army Medical University

摘　　要：目的分析先天性无虹膜1家系遗传学特点,了解PAX6基因突变特点及临床表型的差异。方法收集该家系的病史及临床资料,进行全外显子基因测序检查及数据分析,应用同源建模服务器SWISS-MODEL构建对应的蛋白质模型进行分析。结果本家系中4名发病者均因虹膜缺失存在畏光、睁眼困难症状,相同临床表型为无虹膜、白内障、黄斑中心凹发育不良,还存在个体差异表型。基因检测结果显示:4名发病者均为PAX6基因上c.442_452del:p.M148Afs*48的杂合缺失移码变异,该变异在物种间高度保守。同源建模结果提示突变的PAX6基因最终导致蛋白质构象发生差异变化。结论新发现的PAX6基因变异在发病的家系成员中表型不完全相同,通过同源建模分析增加了对PAX6异常表达导致蛋白质结构异常的认识,遗传学检查可对该家系提供遗传学证据。Objective To analyze the genetic features of congenital aniridia in a family and to explore the characteristics of PAX6 gene mutations and differences in clinical phenotypes.Methods The medical history and clinical data of this family line were collected.Whole-exon gene sequencing and data analysis were performed,and homology modelling server SWISS-MODEL was applied to construct the corresponding protein model for analysis.Results All 4 individuals with onset in this family line had photophobia and difficulty in opening the eyes due to iris deficiency,with the same clinical phenotypes of aniridia,cataracts,and macular centro-concave dysplasia.But,there were still individual differences in phenotypes.Genetic examination showed that all 4 affected individuals were heterozygous for a heterozygous deletion shifted variant c.442_452del:p.M148Afs*48 on the PAX6 gene,which is highly conserved among species.Homozygous modeling suggested that the mutated PAX6 gene ultimately led to differential changes in protein conformation.Conclusion The newly identified PAX6 gene variant is not phenotypically identical among members of the family with congenital aniridia,and homology modeling analysis has increased the understanding that aberrant expression of PAX6 leads to structural abnormalities in the protein.Genetic examination may provide genetic evidence for this family line.

关 键 词：PAX6基因 基因突变 先天性无虹膜 同源建模 

分 类 号：R394.2[医药卫生—医学遗传学] R771.1[医药卫生—基础医学] R773.1