A novel RNA-splicing mutation in TRAPPC2 gene causing X-linked spondyloepiphyseal dysplasia tarda in a large Chinese family

Abstract

X-linked spondyloepiphyseal dysplasia tarda (SEDT; OMIM 313400) is a rare osteochondrodysplasia that occurs in affected individuals between 3 and 12 yr of age. Clinical features include short trunk, barrel-shaped chest and disproportionate short stature. Radiological abnormalities may become evident between 10 and 14 yr of age and include platyspondyly with hump-shaped central and posterior portions of the vertebrae, narrow disc spaces and moderate epiphyseal dysplasia of the long bones, which may be associated with osteoarthritis. Female heterozygous carriers are clinically and radiographically normal. SEDT is caused by mutations in the TRAPPC2 gene, (trafficking protein particle complex 2), which spans a genomic region of ∼20 kb in Xp22. In a large Chinese SEDT family, we screened all the six exons of the TRAPPC2 gene and identified a novel RNA-splicing mutation (IVS4+1A>G). We also demonstrated that the mutation induced splice pattern change from AT/AC to GT/AG. As a result, the first seven nucleotides of exon 5 were spliced out from the transcript. The prediction of the amino acid sequence showed that the seven nucleotides deletion of the transcript caused frame shift and led to premature translation termination, causing loss of two alpha helices. The results of our study expand the spectrum of the gene mutations associated with SEDT, and will help further to elucidate the role of this protein in the etiology of this form of osteochondrodysplasia. X-linked spondyloepiphyseal dysplasia tarda mutations in the TRAPPC2 gene previously identified as SEDL gene,

DOI: 10.1007/s12041-009-0012-3

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Cite this paper

@article{Guo2009ANR, title={A novel RNA-splicing mutation in TRAPPC2 gene causing X-linked spondyloepiphyseal dysplasia tarda in a large Chinese family}, author={Hong Guo and Xueqing Xu and Kai Wang and Bo Zhang and Guo-hong Deng and Yan Wang and Yun Bai}, journal={Journal of Genetics}, year={2009}, volume={88}, pages={87-91} }