先天性挛缩蜘蛛指畸形的临床及遗传学特点
Clinical and genetic characteristics of congenital contractural arachnodactyly
陈丹 1田文 1王树峰 1孙丽颖 1钟文耀 1郭阳 1黄志峰 1赵宗璇 1李清扬 1张楠1
作者信息
摘要
目的 探究先天性挛缩蜘蛛指畸形(congenital contractural arachnodactyly,CCA)的临床特点、遗传学特点及基因-表型相关性.方法 选用我中心就诊 16 例临床诊断为 CCA 并且存在基因 FBN2 突变的患者(男 8 例,女 8 例),平均年龄 5 岁.对既往留存患者信息、临床资料、照片、检查结果以及二代测序检测结果进行回顾,分析总结该 16 例患者的临床表现特征、遗传学特点及二者相关性.结果 16 例中均存在细长指(趾)(16/16,100%)及手部多发关节挛缩(16/16,100%),存在大关节挛缩体征 11 例(11/15,73.3%),肌肉发育不良 14 例(14/16,87.5%),脊柱畸形 5 例(5/14,35.7%),胸廓畸形 6 例(6/15,40.0%),卷曲耳 16 例(16/16,100%),小下颌 9 例(9/16,56.3%),高腭弓 7 例(7/11,63.6%).16 例中共发现 13 种基因 FBN2 突变,位于外显子区域的错义突变 12 种,内含子区域突变 1 种;突变 c.2831G>A 与c.5200+5G>A 为既往文献及相关数据库未报道的新突变位点.突变位点位于外显子 26～29 者多出现大关节挛缩以及脊柱畸形.结论 本组 16 例 CCA 发现了 2 种既往未报道的新位点,并且突变位于外显子 26～29 时,多出现大关节挛缩以及脊柱畸形.
Abstract
Objective To investigate the clinical features,genetic characteristics,and genotype-phenotype correlations of congenital contractural arachnodactyly(CCA).Methods Sixteen patients(8 males and 8 females)with a clinical diagnosis of CCA and a mutation of gene FBN2,with a mean age of 5 years,were enrolled in this research.A retrospective study was conducted to review the previous patient information,clinical data,photographs,examination results,and second-generation sequencing test results,and to analyze and summarize the clinical features,genetic characteristics,and genotype-phenotype correlations.Results Of these 16 patients,all had arachnodactyly(16/16,100%)and multiple joint contractures of the hands(16/16,100%),11 had large joint contractures(11/15,73.3%),14 had muscle hypoplasia(14/16,87.5%),5 had kyphosis/scoliosis(5/14,35.7%),6 had pectus deformity(6/15,40.0%),16 had crumpled ears(16/16,100%),9 had micrognathia(9/16,56.3%),and 7 had highly arched palate(7/11,63.6%).Thirteen different kinds of mutations in gene FBN2 were identified in 16 patients,with 12 missense mutations located in exons and 1 mutation in introns.The mutations c.2831G>A and c.5200+5G>A were new mutations not reported before.In addition,this study found that patients with mutations in exons 26-29 are more likely to have large joint contractures and spinal deformities.Conclusions This study summarizes the clinical manifestations of 16 CCA patients and identifies 2 unreported mutations,and patients with mutations in exons 26-29 were more likely to have large joint contractures and spinal deformities.
关键词
蜘蛛样指(趾)/肢畸形,先天性/指/关节挛缩/Beals综合征Key words
Arachnodactyly/Limb deformities,congenital/Fingers/Arthrogryposis/Beals syndrome引用本文复制引用
基金项目
国家重点研发计划-罕见病临床队列研究-精准医学研究专项(2016YFC0901500)
北京积水潭医院"学科新星"计划(XKXX202201)
首都卫生发展科研专项(首发-2022-2-2072)
出版年
2024
NETL
NSTL
万方数据