Abstract
Treacher Collins syndrome (TCS) is the most common and well-known craniofacial disorder caused by mutations in the genes involved in pre-rRNA transcription, which include the TCOF1 gene. This study explored the role of TCOF1 mutations in Chinese patients with TCS. Mutational analysis of the TCOF1 gene was performed in three patients using polymerase chain reaction and direct sequencing. Among these three patients, two additional TCOF1 variations, a novel 18 bp deletion and a novel 1 bp insertion mutation, were found in patient 1, together with a novel nonsense mutation (p.Ser476X) and a previously reported 4 bp deletion (c.1872_1875delTGAG) in other patients. Pedigree analysis allowed for prediction of the character of the mutation, which was either pathological or not. The 18 bp deletion of six amino acids, Ser-Asp-Ser-Glu-Glu-Glu (798*803), which was located in the CKII phosphorylation site of treacle, seemed relatively benign for TCS. By contrast, another novel mutation of c.1072_1073insC (p.Gln358ProfsX23) was a frameshift mutation and expected to result in a premature stop codon. This study provides insights into the functional domain of treacle and illustrates the importance of clinical and family TCS screening for the interpretation of novel sequence alterations.
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Acknowledgments
We thank all the tested individuals, their families, and collaborating clinicians for their participation. This work was supported by the National Natural Science Foundation of China (81300527).
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The authors declare no conflict of interest.
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Communicated by S. Hohmann.
Y. Wang, X.-J. Yin and T. Han have contributed equally to the paper.
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Wang, Y., Yin, XJ., Han, T. et al. A novel silent deletion, an insertion mutation and a nonsense mutation in the TCOF1 gene found in two Chinese cases of Treacher Collins syndrome. Mol Genet Genomics 289, 1237–1240 (2014). https://doi.org/10.1007/s00438-014-0883-8
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DOI: https://doi.org/10.1007/s00438-014-0883-8