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

BACKGROUND: Congenital 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 PRESENTATION: In 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. CONCLUSIONS: This study has identified a novel missense mutation in FBN2 gene (p.C1077G) resulting in CCA in a family of China.