七个睑裂狭小综合征家系的表型及变异分析  

Phenotype and genetic variant analysis of seven pedigrees affected with blepharophimosis syndrome

作　　者：白周现 刘莉娜 孔祥东[1] Bai Zhouxian;Liu Lina;Kong Xiangdong(Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2021年第11期1060-1063,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002206-2);郑州大学第一附属医院青年创新基金(YNQN2017008)。

摘　　要：目的分析先天性睑裂狭小综合征(blepharophimosis,ptosis and epicanthus inversus syndrome,BPES)患者的临床表现和基因变异,为临床诊断确诊提供依据。方法收集7个BPES家系的临床资料,采集患者及其家系成员的外周血样,提取基因组DNA。应用Sanger测序筛查FOXL2基因的全部外显子区域,对结果为阴性的家系进行二代测序和基因组拷贝数变异检测。查询相关数据库和PubMed检索相关变异的致病性,利用蛋白质预测软件阐释其功能。结合患者的眼部外观、病史和基因变异进行分析。结果在6个家系中找到了致病变异,其中4个为已知变异、1个为既往未见报道的FOXL2基因c.299dupA(p.Asn100Lysfs*2)变异、1个为涉及FOXL2基因的染色体3q22.3q23区杂合缺失。FOXL2基因c.299dupA移码变异可能导致蛋白质翻译提前终止,为致病性变异。结论综合运用Sanger测序、二代测序及微阵列芯片检测,明确了6个BPES家系的致病变异,为相关家系的遗传咨询和产前诊断提供了依据。Objective To analyze the clinical manifestations and gene variants of patients with blepharophimosis,ptosis and epicanthus inversus syndrome(BPES).Methods Clinical data of 7 pedigrees affected with BPES were collected,and genomic DNA was extracted from peripheral blood samples of the probands and their relatives.All exons of the FOXL2gene were subjected to Sanger sequencing.Those with negative findings were further screened by targeted capture and next generation sequencing(NGS)and microarray analysis.Pathogenicity of candidate variants were predicted by search of PubMed and related databases,and the impact of the variants was interpreted by protein prediction software.Diagnosis was confirmed by clinical phenotype,medical history and mutation analysis.Results A pathogenic variant was identified in six of the 7 pedigrees,which included four known pathogenic variants and one novel FOXL2 c.299dupA variant.A heterozygous 3q22.3q23 deletion,which encompassed the FOXL2 gene,was identified in another pedigree.As predicted,the c.299dupA frameshift mutation of FOXL2 gene can lead to the premature termination of protein translation,which is pathogenic.Conclusion A novel and 5 known pathogenic variants have been identified in six pedigrees affected with BPES by the combined Sanger sequencing,target capture NGS and microarray analysis.Above findings have enabled genetic counseling and prenatal diagnosis for these pedigrees.

关 键 词：睑裂狭小 靶向测序 FOXL2基因 分子诊断 

分 类 号：R777.1[医药卫生—眼科]