title: Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing.
abstract: Congenital contractural arachnodactyly (CCA, OMIM 121050), also known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, dolichostenomelia, pectus deformities, kyphoscoliosis, congenital contractures and a crumpled appearance of the helix of the ear. The aim of this study is to identify the genetic cause of a 4-generation Chinese family of Tujia ethnicity with congenital contractural arachnodactyly by exome sequencing. The clinical features of patients in this family are consistent with CCA. A novel missense mutation, c.3769T>C (p.C1257R), in the fibrillin 2 gene (FBN2) was identified responsible for the genetic cause of our family with CCA. The p.C1257R mutation occurs in the 19th calcium-binding epidermal growth factor-like (cbEGF) domain. The amino acid residue cysteine in this domain is conserved among different species. Our findings suggest that exome sequencing is a powerful tool to discover mutation(s) in CCA. Our results may also provide new insights into the cause and diagnosis of CCA, and may have implications for genetic counseling and clinical management.
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.|Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.|Department of Medical Information, Information Security and Big Data Research Institute, Central South University, Changsha, 410013, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Qiongfen
authors.initials: Q
authors.lastname: Lin
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Song
mesh_terms: D000328:Adult; D054119:Arachnodactyly / Q000235:genetics*; D002681:China; D003286:Contracture / Q000235:genetics*; D059472:Exome; D005260:Female; D000071840:Fibrillin-2 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C000605723:FBN2 protein, human; D000071840:Fibrillin-2