Frontiers in Genetics (Mar 2022)
Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly
- Liying Sun,
- Yingzhao Huang,
- Yingzhao Huang,
- Yingzhao Huang,
- Sen Zhao,
- Sen Zhao,
- Sen Zhao,
- Wenyao Zhong,
- Jile Shi,
- Jile Shi,
- Jile Shi,
- Yang Guo,
- Junhui Zhao,
- Ge Xiong,
- Yuehan Yin,
- Zefu Chen,
- Zefu Chen,
- Zefu Chen,
- Nan Zhang,
- Zongxuan Zhao,
- Qingyang Li,
- Dan Chen,
- Yuchen Niu,
- Yuchen Niu,
- Xiaoxin Li,
- Xiaoxin Li,
- Guixing Qiu,
- Guixing Qiu,
- Guixing Qiu,
- Zhihong Wu,
- Zhihong Wu,
- Zhihong Wu,
- Terry Jianguo Zhang,
- Terry Jianguo Zhang,
- Terry Jianguo Zhang,
- Wen Tian,
- Nan Wu,
- Nan Wu,
- Nan Wu
Affiliations
- Liying Sun
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Yingzhao Huang
- 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
- Yingzhao Huang
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Yingzhao Huang
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Sen Zhao
- 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
- Sen Zhao
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Sen Zhao
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Wenyao Zhong
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Jile Shi
- 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
- Jile Shi
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Jile Shi
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Yang Guo
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Junhui Zhao
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Ge Xiong
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Yuehan Yin
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Zefu Chen
- 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
- Zefu Chen
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Zefu Chen
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Nan Zhang
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Zongxuan Zhao
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Qingyang Li
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Dan Chen
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Yuchen Niu
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Yuchen Niu
- State Key Laboratory of Complex Severe and Rare Diseases, Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Xiaoxin Li
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Xiaoxin Li
- State Key Laboratory of Complex Severe and Rare Diseases, Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Guixing Qiu
- 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
- Guixing Qiu
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Guixing Qiu
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Zhihong Wu
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Zhihong Wu
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Zhihong Wu
- State Key Laboratory of Complex Severe and Rare Diseases, Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Terry Jianguo Zhang
- 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
- Terry Jianguo Zhang
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Terry Jianguo Zhang
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- Wen Tian
- Department of Hand Surgery, Clinical and Research Center for Congenital Hand Deformities and Rare Diseases, Beijing Jishuitan Hospital, Beijing, China
- Nan Wu
- 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
- Nan Wu
- Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China
- Nan Wu
- Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, China
- DOI
- https://doi.org/10.3389/fgene.2022.804202
- Journal volume & issue
-
Vol. 13
Abstract
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 FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 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 FBN2 and ANKRD11 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.
Keywords
- FBN2 (fibrillin-2)
- congenital contractural arachnodactyly
- arthrogryposis
- novel variants
- clinical genetics
- musculo-skeletal diseases
