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Background <p>Treacher Collins syndrome (TCS) is a congenital disorder primarily caused by the mutation in the Treacle Ribosome Biogenesis Factor 1 (<i>TCOF1</i>) gene. However, the significance of many <i>TCOF1</i> mutations remains uncertain.</p> Results <p>We report two novel mutations identified in two TCS families and assess their pathogenicity alongside two previously reported mutations. Both novel mutations, c.2115dupG (p.T706DfsTer52) and c.2142+23_2142+52 del (p.A715VfsTer31), result in truncated proteins lacking nuclear location signals (NLSs), which impedes their entry into the nucleus and reduces mRNA expression level. Notably, the mutation c.2142+23_2142+52 del, leading to the retention of a 62 bp intron and disrupting RNA splicing, represents the first documented case of intron retention in TCS patients. Additionally, the previously reported mutation c.136&#xa0;C&gt;&#xa0;G (p.L46V) hinders protein nuclear location, while mutation c.1719del (p.N574TfsTer22) significantly decreases mRNA levels.</p> Conclusions <p>Our research expands the spectrum of <i>TCOF1</i> mutations and provides evidence clarifying their pathogenic nature. These findings are crucial for genetic counseling and prenatal diagnosis for TCS patients.</p>

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Identification of novel TCOF1 mutations in Treacher Collins syndrome and their functional characterization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月16日

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  • Ying Chen,
  • Run Yang,
  • Xin Chen,
  • Tianyu Zhang,
  • Chenlong Li,
  • Jing Ma

摘要

Background

Treacher Collins syndrome (TCS) is a congenital disorder primarily caused by the mutation in the Treacle Ribosome Biogenesis Factor 1 (TCOF1) gene. However, the significance of many TCOF1 mutations remains uncertain.

Results

We report two novel mutations identified in two TCS families and assess their pathogenicity alongside two previously reported mutations. Both novel mutations, c.2115dupG (p.T706DfsTer52) and c.2142+23_2142+52 del (p.A715VfsTer31), result in truncated proteins lacking nuclear location signals (NLSs), which impedes their entry into the nucleus and reduces mRNA expression level. Notably, the mutation c.2142+23_2142+52 del, leading to the retention of a 62 bp intron and disrupting RNA splicing, represents the first documented case of intron retention in TCS patients. Additionally, the previously reported mutation c.136 C> G (p.L46V) hinders protein nuclear location, while mutation c.1719del (p.N574TfsTer22) significantly decreases mRNA levels.

Conclusions

Our research expands the spectrum of TCOF1 mutations and provides evidence clarifying their pathogenic nature. These findings are crucial for genetic counseling and prenatal diagnosis for TCS patients.