Ehlers-Danlos综合征的临床遗传学研究进展  

Advances in Clinical Genetics of the Ehlers-Danlos Syndromes

作　　者：徐可欣 李国壮 李晴 尹相杰 方堃 吴志宏 仉建国[1,2,3] 系统解析脊柱侧凸及相关合并症(DISCO)国际多中心协作组 吴南 XU Kexin;LI Guozhuang;LI Qing;YIN Xiangjie;FANG Kun;WU Zhihong;ZHANG Jianguo;DISCO(Deciphering Disorders Involving Scoliosis&COmorbidities)Study Group;WU Nan(Department of Orthopedic Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Beijing Key Laboratory for Genetic Research of Skeletal Deformity,Key Laboratory of Big Data for Spinal Deformities,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Medical Science Research Center(MRC),Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;不详)

机构地区：[1]中国医学科学院北京协和医院骨科,北京100730 [2]中国医学科学院北京协和医院骨骼畸形遗传学研究北京市重点实验室、中国医学科学院脊柱畸形大数据研究与应用重点实验室,北京100730 [3]中国医学科学院北京协和医院疑难重症及罕见病全国重点实验室,北京100730 [4]中国医学科学院北京协和医院医学科学研究中心,北京100730 [5]不详

出　　处：《罕见病研究》2024年第3期295-303,共9页Journal of Rare Diseases

基　　金：国家重点研发计划(2022YFC2703102,2022YFC2703901);中央高水平医院临床科研业务费(2022-PUMCH-D-004,2022-PUMCH-C-033);中国医学科学院医学与健康科技创新工程(2021-I2M-1-051,2021-I2M-1-052,2022-I2M-2-001,2023-I2M-C&T-A-003)。

摘　　要：Ehlers-Danlos综合征(EDS)是一组罕见的遗传性结缔组织疾病,以关节过度活动、皮肤过度伸展和组织脆弱为主要特征。EDS的临床和遗传异质性较强,误诊、漏诊均较为常见,基因检测是明确诊断的重要方式。EDS部分亚型已有初步的基因型-表型关联研究结果,或是引入了疾病谱系的概念。这些研究加深了病因学理解,对临床疾病管理起到一定提示作用。2023年发布的《中国Ehlers-Danlos综合征诊疗指南》推荐对达到临床诊断标准或疑诊EDS的患者结合深度表型评估进行基因检测。但应当注意,患者的临床诊断与分子诊断可能并不一致。此外,对于未获得明确分子诊断的患者,可考虑通过定期数据重分析、整合RNA测序与家系全基因组测序、第三代测序等方式寻找致病性变异。本文简要概括EDS的临床遗传学研究进展,为临床诊疗和科研工作提供参考,最大程度提高EDS患者的生活质量。The Ehlers-Danlos syndromes(EDS)are a group of rare hereditary connective tissue disorders characterized by joint hypermobility,skin hyperextensibility,and tissue fragility.The clinical and genetic hetero-geneity of EDS frequently leads to underdiagnosis and misdiagnosis.Genetic testing is an essential approach to clarify the underlying diagnosis.Recent research has preliminarily established genotype-phenotype correlations and introduced the novel concept of"disease spectrum"in some subtypes.These studies deepen our understanding of EDS etiology and provide important insights into clinical management.Published in 2023,the Chinese Guidelines for Diagnosis and Treatment of the Ehlers-Danlos Syndromes(the Guidelines)recommend performing genetic testing with deep phenotyping for patients who meet the clinical diagnostic criteria or are suspected of having EDS.However,it should be noted that the clinical diagnosis might differ from the molecular diagnosis.Furthermore,cutting-edge approaches such as periodic data reanalysis,integration of RNA sequencing into family-based whole-genome sequencing,and third-generation sequencing may facilitate the reclassification of variants of uncertain significance or resolve undiagnosed cases.This article summarizes recent progress in the genetics research of EDS,with the hope of offering a valuable resource for clinical diagnosis,treatment and scientific research to optimize the quality of life of patients with EDS.

关 键 词：EHLERS-DANLOS综合征 临床遗传学 基因型-表型关联 全基因组测序 RNA测序 深度表型评估 

分 类 号：R593.2[医药卫生—内科学]