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Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations

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Abstract

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype–genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon–intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

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Correspondence to Gang Chai or Tian-yu Zhang.

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Conflict of interest

All the authors declare that they have no conflict of interest.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81570934), 973 Project (No. 2011CB504501) and Shanghai Hospital Development Center (No. 16CR2010A).

Ethical standards

This study was approved by the local ethical committee. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all participants whose photos are presented in this article.

Additional information

Communicated by S. Hohmann.

The first two authors contributed equally to this work.

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Chen, Y., Guo, L., Li, Cl. et al. Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations. Mol Genet Genomics 293, 569–577 (2018). https://doi.org/10.1007/s00438-017-1384-3

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  • DOI: https://doi.org/10.1007/s00438-017-1384-3

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