Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing.

Hao Deng,Qiongfen Lin,Zhijian Yang,Lamei Yuan,Qian Lu,Xiong Deng,Jingjing Xiao,Hongbo Xu,Liping Guan,Zhi Song,Yi Guo,Zhi-Ying Wu

doi:10.1371/journal.pone.0155908

Hao Deng, Qiongfen Lin + Show 10 more

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https://doi.org/10.1371/journal.pone.0155908

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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.

Highlights

Congenital contractural arachnodactyly (CCA, OMIM 121050), known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue
We found a heterozygous c.3769T>C transition (p.C1257R), which co-segregates with patients in this family and are absent in normal controls, in the fibrillin 2 gene (FBN2) gene
CCA is phenotypically related to Marfan syndrome (MFS), including tall stature, marfanoid habitus, arachnodactyly, camptodactyly, kyphoscoliosis and pectus excavatum [22]

Summary

Introduction

Congenital contractural arachnodactyly (CCA, OMIM 121050), known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is phenotypically related to but genetically distinct from Marfan syndrome (MFS) [1]. It was first introduced by Rodney Beals and Frederick Hechet in 1971. It is characterized by contractures, arachnodactyly, narrow body habitus, elongated limbs, chest wall deformities, scoliosis, muscular hypoplasia and crumpled ears [2,3]. It can be divided into classical CCA and severe/lethal CCA. Patients with severe/lethal CCA show cardiac abnormalities (mitral valve prolapse, atrial septal defect, ventricular septal defect and aortic hypoplasia) and gastrointestinal anomalies

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