一单纯性晶状体异位家系的基因型及临床表型研究  

Study on the genotype and clinical phenotype of a family with isolated ectopia lentis

作　　者：王书军 叶敏捷[1] 范玲玲 廖荣丰[1] Wang Shujun;Ye Minjie;Fan Lingling;Liao Rongfeng(Dept of Ophthalmology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院眼科,合肥230022

出　　处：《安徽医科大学学报》2024年第5期898-903,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1908085QH381)。

摘　　要：目的对一单纯性晶状体异位(IEL)家系患者的致病基因进行筛查,并分析该家系临床特征。方法该研究纳入一IEL家系共5代48例成员。收集家系成员外周血样本,并通过全身体格检查及眼科常规检查观察临床表现特点。采用全外显子组测序(WES)技术对家系中2例患者进行致病基因筛查。通过对家系其他成员及200例正常对照人群进行基因靶向Sanger测序验证。并采用SIFT、PolyPhen和MutationTester软件预测蛋白功能。结果该家系共13例IEL患者,以常染色显性模式遗传,平均发病年龄为51.5岁。临床特征主要为晶状体异位伴前倾向前房,前房变浅,房角变窄,最终导致继发性青光眼。通过筛选及验证显示家系所有患者均携带原纤维蛋白基因-1(FBN1)基因c.3463G>A突变,在200例对照人群中未发现该突变。SIFT、PolyPhen和MutationTester功能预测软件均提示该突变影响蛋白功能。结论该IEL主要临床表型是晶状体异位伴前倾导致继发性青光眼。FBN1基因的c.3463G>A可能是导致该家系IEL的致病突变。Objective To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis(IEL).Methods Forty-eight members with 5 generations of an IEL family were enrolled in this study.Peripheral blood samples of all members were collected,and clinical manifestations were observed through physical examination and routine ophthalmological examination.Whole-exome sequencing(WES)was performed for two patients to identify disease-causing variants.The target variants were verified by Sanger sequencing in family members and 200 normal controls.Then,candidate variants were verified using Sanger sequencing in family members and 200 healthy controls.SIFT,PolyPhen and MutationTester were used to predict the protein function.Results A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern.The mean age at disease onset was 51.5 years.The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber.As the anterior chamber became shallow,and the angle of the chamber became narrow,and eventually resulted in the secondary glaucoma.A heterozygous missense variant in the fibrillin gene-1(FBN1)gene(c.3463G>A)was identified by WES,which was present in all patients but was absent in 200 healthy controls.SIFT,PolyPhen and MutationTester predicted that the variant affected protein function.Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination.The c.3463G>A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

关 键 词：晶状体异位 原纤维蛋白基因-1 马凡综合征 全外显子组测序 Sanger测序 

分 类 号：R776.2[医药卫生—眼科]