Sun Liying, Huang Yingzhao, Zhao Sen, Zhong Wenyao, Shi Jile, Guo Yang, Zhao Junhui, Xiong Ge, Yin Yuehan, Chen Zefu, Zhang Nan, Zhao Zongxuan, Li Qingyang, Chen Dan, Niu Yuchen, Li Xiaoxin, Qiu Guixing, Wu Zhihong, Zhang Terry Jianguo, Tian Wen, Wu Nan
Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China.
Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Front Genet. 2022 Mar 10;13:804202. doi: 10.3389/fgene.2022.804202. eCollection 2022.
Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients' blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported variants were identified through exome sequencing. Two variants outside of the neonatal region of gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of and in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.
先天性挛缩性蜘蛛指（趾）症（CCA）是一种罕见的常染色体显性结缔组织疾病，其特征为耳朵皱缩、蜘蛛指（趾）、屈曲指、大关节挛缩和脊柱侧凸。CCA的自然病程尚未得到充分描述。我们旨在解读CCA的遗传和表型谱。该队列是基于“解读涉及脊柱侧凸及合并症（DISCO）研究”（http://www.discostudy.org/）在中国北京积水潭医院和北京协和医院招募的。对患者的血液DNA进行外显子组测序。在我们的队列中验证了最近发表的CCA评分系统。通过外显子组测序鉴定出7个新变异和3个先前报道的变异。在基因的新生儿区域之外发现了两个变异。我们队列中的患者与先前文献中的患者在表型上具有可比性，几乎所有患者都有蜘蛛指（趾）、屈曲指和大关节挛缩。根据CCA评分系统，所有符合分析条件的患者均成功分类为可能的CCA。此外，我们在一名具有由CCA和KBG综合征组成的混合表型的患者中发现了和的双重致病杂合变异。7个新变异的鉴定拓宽了CCA的突变和表型谱，可能为遗传咨询和临床管理提供启示。
