Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural ArachnodactylyReportar como inadecuado


Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly


Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

2

Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200127, China

3

Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 200127, China

4

Department of Pediatric Orthopedics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China



These authors contributed equally to this work.





*

Authors to whom correspondence should be addressed.



Academic Editor: Emil Alexov

Abstract Congenital contractural arachnodactyly CCA is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, camptodactyly, contrature of major joints, scoliosis, pectus deformities, and crumpled ears. The present study aimed to identify the genetic cause of a three-generation Chinese family with CCA. We successfully identified a novel missense mutation p.G1145D in the fibrillin-2 FBN2 gene as the pathogenic mutation by whole exome sequencing WES. The p.G1145D mutation occurs in the 12th calcium-binding epidermal growth factor-like cbEGF domain. The p.G1145D mutation caused a hydrophobic to hydrophilic substitution, altering the amino acid property from neutral to acidic. Three-dimensional structural analysis showed that this mutation could alter the conformation of the residue side chain, thereby producing steric clashes with spatially adjacent residues, disrupting the formation of H bonds and causing folding destabilization. Therefore, this amino acid appears to play an important role in the structure and function of FBN2. Our results may also provide new insights into the cause and diagnosis of CCA and may have implications for genetic counseling and clinical management. View Full-Text

Keywords: congenital contractural arachnodactyly; exome sequencing; fibrillin-2 FBN2 gene congenital contractural arachnodactyly; exome sequencing; fibrillin-2 FBN2 gene





Autor: Guoling You 1,†, Bailing Zu 2,3,†, Bo Wang 1, Zhigang Wang 4, Yunlan Xu 4,* and Qihua Fu 1,*

Fuente: http://mdpi.com/



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