Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly

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...

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Published in:Frontiers in genetics 2022-03, Vol.13, p.804202-804202
Main Authors: 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
Format: Article
Language:English
Subjects:
arthrogryposis
clinical genetics
congenital contractural arachnodactyly
FBN2 (fibrillin-2)
Genetics
musculo-skeletal diseases
novel variants
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Summary: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.
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2022.804202