AUTHOR=Xu Peiwen , Li Ruirui , Huang Sexin , Sun Menghan , Liu Jiaolong , Niu Yuping , Zou Yang , Li Jie , Gao Ming , Li Xiaolei , Gao Xuan , Gao Yuan TITLE=A Novel Splicing Mutation in the FBN2 Gene in a Family With Congenital Contractural Arachnodactyly JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00143 DOI=10.3389/fgene.2020.00143 ISSN=1664-8021 ABSTRACT=

Congenital contractural arachnodactyly (CCA) is an extremely rare monogenic disorder in humans, and the prevalence of CCA is estimated to be less than 1 in 10,000 worldwide. CCA is characterized by arachnodactyly, camptodactyly, the contracture of major joints, scoliosis, pectus deformities, and crumpled ears. Mutations in FBN2 (which encodes fibrillin-2) are responsible for causing this disease. A family with CCA was investigated in this study, and a novel variant, c.3724+3A > C (also identified as IVS28+3A > C), in FBN2 was found in nine patients from the family but was not found in seven unaffected relatives. Reverse transcription-PCR (RT-PCR) and complementary DNA (cDNA) sequencing data showed that exon 28 was skipped in the FBN2 gene. The FBN2 c.3724+3A > C variant led to an in-frame deletion during transcription, which eventually triggered CCA in the Chinese family.