吴南;李国壮;吴志宏;仉建国;邱贵兴;
WU Nan;LI Guozhuang;WU Zhihong;ZHANG Jianguo;QIU Guixing;Department of Orthopaedic Surgery,Chinese Academy of Medical Sciences & Peking Union Medical College;Beijing Key Laboratory for Genetic Research of Skeletal Deformity,Chinese Academy of Medical Sciences & Peking Union Medical College;Key Laboratory of Big Data for Spinal Deformities,Chinese Academy of Medical Sciences & Peking Union Medical College;State Key Laboratory of Complex Severe and Rare Diseases,Chinese Academy of Medical Sciences

• 1:中国医学科学院北京协和医院骨科
• 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
• 3:中国医学科学院北京协和医院脊柱畸形大数据研究与应用重点实验室
• 4:中国医学科学院北京协和医院疑难重症及罕见病国家重点实验室

摘要(Abstract)：

先天性脊柱侧凸(congenital scoliosis, CS)是起源于胚胎期脊柱发育异常的先天性脊柱畸形，具有进展快、畸形重、并发症多等特点，给患者及家庭带来了沉重的经济和精神负担。目前，对于脊柱畸形的病因学治疗尚无良策。因缺乏早期预测手段，患者多在出现畸形外观时才被发现，治疗方法多以支具或手术控制病情发展的被动、保守或创伤性治疗为主。因此，探索脊柱畸形早期的诊断方法和有效的病因学干预靶点是当前国际研究的热点。近10年来，北京协和医院骨科团队专注于CS的分子遗传学研究和临床应用，牵头建立了国际多中心骨骼畸形遗传研究体系；通过大规模队列研究，发现并论证了TBX6基因无效变异联合常见亚效等位基因共同导致CS,建立了一套基因型-表型整合分析方法，成功定义了一种全新的CS疾病亚型——TBX6相关先天性脊柱侧凸，并实现了临床对于这一独特亚型的精准预测；率先开设骨骼畸形遗传门诊，实现研究成果的临床转化，为骨骼畸形病因学研究及临床应用提供了新范式。
Congenital scoliosis(CS) is a congenital spinal deformity that originates from abnormal spinal development in embryo. Characterized by rapid progression, severe deformity, and many complications, CS brings heavy economic and mental burden to patients and their families. At present, there is no good treatment for the etiology of spinal deformity. Due to the lack of early prediction methods, patients are often not detected until the appearance of malformation, and the treatment is mainly passive, conservative or traumatic treatment with braces or surgery to control the progression of the disease. Therefore, the exploration of early diagnosis methods and effective etiological intervention targets for spinal deformity is currently an international research hotspot. The orthopaedic team of Peking Union Medical College Hospital, focusing on the molecular genetics research and clinical application of CS, has built the world leading genetic research system of skeletal deformity. Through a multi-center large-scale cohort study, the team has found and demonstrated that compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 led to CS. A set of genotype-phenotype integrated analysis method has been established, which successfully defined a new subtype of CS(TBX6-associated congenital scoliosis, TACS) and realized accurate clinical prediction of this unique subtype. With the establishment of the first genetics clinic of skeletal deformity in China, the clinical transformation of research results can thus be realized, providing a new paradigm for the etiology research and clinical application of skeletal deformity.

关键词(KeyWords)： 先天性脊柱侧凸;TBX6;TBX6相关先天性脊柱侧凸;分子遗传学;临床应用
congenital scoliosis;TBX6;TBX6-associated congenital scoliosis;molecular genetics;clinical practice

Abstract:

Keywords:

基金项目(Foundation): 中国医学科学院医学与健康科技创新工程(2021-I2M-1-051,2021-I2M-1-052,2020-I2M-C&T-B-030);; 中央级公益性科研院所基本科研项目(2019PT320025)~~

作者(Authors): 吴南;李国壮;吴志宏;仉建国;邱贵兴;
WU Nan;LI Guozhuang;WU Zhihong;ZHANG Jianguo;QIU Guixing;Department of Orthopaedic Surgery,Chinese Academy of Medical Sciences & Peking Union Medical College;Beijing Key Laboratory for Genetic Research of Skeletal Deformity,Chinese Academy of Medical Sciences & Peking Union Medical College;Key Laboratory of Big Data for Spinal Deformities,Chinese Academy of Medical Sciences & Peking Union Medical College;State Key Laboratory of Complex Severe and Rare Diseases,Chinese Academy of Medical Sciences

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