Whole exome sequencing identifies a novel missense FBN2 mutation co-segregating in a four-generation Chinese family with congenital contractural arachnodactyly

Abstract

BackgroundCongenital contractural arachnodactyly (CCA) is an autosomal dominant rare genetic disease, estimated to be less than 1 in 10,000 worldwide. People with this condition often have permanently bent joints (contractures), like bent fingers and toes (camptodactyly).Case presentationIn this study, we investigated the genetic aetiology of CCA in a four-generation Chinese family. The blood samples were collected from 22 living members of the family in the Yangquan County, Shanxi Province, China. Of those, eight individuals across 3 generations have CCA. Whole exome sequencing (WES) identified a missense mutation involving a T-to-G transition at position 3229 (c.3229 T > G) in exon 25 of the FBN2 gene, resulting in a Cys 1077 to Gly change (p.C1077G). This previously unreported mutation was found in all 8 affected individuals, but absent in 14 unaffected family members. SIFT/PolyPhen prediction and protein conservation analysis suggest that this novel mutation is pathogenic. Our study extended causative mutation spectrum of FBN2 gene in CCA patients.ConclusionsThis study has identified a novel missense mutation in FBN2 gene (p.C1077G) resulting in CCA in a family of China.

Comparative iTRAQ proteomics revealed proteins associated with horn development in yak

“…Fibrillin 2 (FBN2) regulates tissue elasticity. Mutations in the FBN2 gene are associated with congenital contractual arachnodactyly (CCA), a condition characterized by dolichostenomelia, pectus deformities, kyphoscoliosis, and congenital contractures [ 32 ]. Gap junction alpha 1 protein (GJA1) is one of the most potent gap junction proteins important for osteoblast differentiation and bone formation.…”

A novel FBN2 mutation cosegregates with congenital contractural arachnodactyly in a five‐generation Chinese family

“…Congenital contractural arachnodactyly is a rare autosomal dominant disorder and has been reported to have various clinical manifestations and intragenic heterogeneity . CCA is genetically distinct from MFS.…”

“…CCA is genetically distinct from MFS. CCA has only been observed in individuals with mutations in FBN2 ; however, individuals with MFS have mutations in FBN1 , TGFBR2 , and TGFBR1 …”

“…Through genetic linkage analysis and mutation screening, FBN2 gene mutations were found to correspond to the incidence of CCA in many probands or families . To date, FBN2 is the only known susceptibility gene of CCA . The FBN2 gene encodes fibrillin‐2, which has been demonstrated to have important roles in the structure of extracellular microfibrils in elastic fiber by providing strength and flexibility to connective tissue .…”

“…To date, FBN2 is the only known susceptibility gene of CCA . The FBN2 gene encodes fibrillin‐2, which has been demonstrated to have important roles in the structure of extracellular microfibrils in elastic fiber by providing strength and flexibility to connective tissue . Previous studies in mouse models showed that the knockout of FBN2 resulted in phenotypes such as forelimbs contractures, disorganized microfibrils, and bilateral syndactyly …”