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Int. J. Mol. Sci. 2017, 18(4), 626; doi:10.3390/ijms18040626

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

1,†
,
2,3,†
,
1
,
4
,
4,* and 1,*
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
Received: 6 February 2017 / Revised: 26 February 2017 / Accepted: 10 March 2017 / Published: 5 April 2017
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
View Full-Text   |   Download PDF [8616 KB, uploaded 5 April 2017]   |  

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
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You, G.; Zu, B.; Wang, B.; Wang, Z.; Xu, Y.; Fu, Q. Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly. Int. J. Mol. Sci. 2017, 18, 626.

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