挛缩性蜘蛛指（趾）综合征一家系临床及FBN2基因变异分析  

Analysis of clinical manifestations and genetic mutations in a family with congenital contractural arachnodactyly

作　　者：罗燕飞[1] 李娟[2] 米热古丽·买买提[1] 王秀敏[2] 王剑[2] LUO Yanfei;LI Juan;MIREGULI Maimaiti;WANG Xiuming;WANG Jian(First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang,China;Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200127,China)

机构地区：[1]新疆医科大学第一附属医院儿科,新疆乌鲁木齐830054 [2]上海交通大学医学院附属上海儿童医学中心内分泌遗传代谢科,上海200127

出　　处：《临床儿科杂志》2019年第11期843-846,共4页Journal of Clinical Pediatrics

基　　金：国家自然科学基金（No.81360139）;上海市浦东新区科技发展基金（PKJ2018-Y46）

摘　　要：目的分析挛缩性蜘蛛指(趾)综合征的临床特征及基因突变特点。方法回顾分析挛缩性蜘蛛指(趾)综合征一家系的临床特点及基因检测结果。结果先证者女,3岁10个月,出生时有蜘蛛样指、双侧肘关节不能活动;父亲、爷爷、曾祖母有同样的表型。先证者及家系中未观察到神经、心血管异常,外耳畸形、听力减退或眼睛异常等。不同性别间的表型及家族成员的表型无显著异质性。提取患儿及其父母、祖父母等外周血DNA行高通量测序,并以Sanger测序进行验证。结果显示先证者FBN2基因错义杂合变异c.244G>A(p.Val82Met),先证者父亲、爷爷、曾祖母携带该变异位点。经Alamut功能软件预测,该变异位点可能会影响蛋白结构域功能,按照ACMG变异分类标准,归类为“可能致病性变异”。结论确诊这一挛缩性蜘蛛指(趾)综合征家系的致病基因为FBN2。Objective To explore the clinical feature,gene mutations of congenital contractural arachnodactyly(CCA).Methods The clinical data from a girl of CCA and her families were retrospectively analyzed.The related literatures were reviewed.Gene sequencing was carried out by high-throughput sequencing and validated by Sanger sequencing.Results A 3-year-10-month old girl was born with arachnodactyly,and inability to move her bilateral elbows.Her father,grandfather and great grandmother showed the same phenotype with her.The proband and other relevant families were not observed with abnormal nervous system,cardiovascular,and external ear deformity or eyes.Phenotypic variability within the family members and different gender was not observed.Gene sequencing identified a missense mutation c.244 G>A(p.Val82Met,heterozygous)in FBN2 gene in the proband and her father,grandfather,and great grandmother.Alamut software predicted that this mutation may affect the function of the protein structure domain.According to the ACMG variation classification criteria,this mutation was classified as"likely pathogenic".Conclusion The diagnosis of CCA caused by FBN2 mutation can be confirmed by highthroughput sequencing technology.

关 键 词：挛缩性蜘蛛指(趾)综合征 靶向基因测序 FBN2基因 

分 类 号：G62[文化科学—教育学]