CASE REPORT article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 13 - 2025 | doi: 10.3389/fped.2025.1615309
Case Report: A Novel Heterozygous Variant of the TCOF1 Gene in Treacher Collins Syndrome
Provisionally accepted
- Lanzhou University Second Hospital, Lanzhou, China
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Treacher Collins syndrome (TCS) is a craniofacial malformation caused by the abnormal development of the first and second pharyngeal arches during embryogenesis. While pathogenic variants in POLR1B, POLR1C, and POLR1D are implicated, the TCOF1 gene represents the primary causative locus. This case report descripts a novel heterozygous frameshift variant, TCOF1:NM_001135243.2:c.3559delG (p.Ala1187GlufsTer21), identified in a child with TCS. This truncation disrupts the C-terminal nuclear localization signal (NLS), specifically ablating a phosphorylation site at residues 1199-1200. Consequently, ribosome biosynthesis and craniofacial neural crest cell development are impaired, culminating in characteristic clinical manifestations, including downslanting palpebral fissures, depressed nasal bridge, marked malar hypoplasia, mandibular hypoplasia, and microtia. Although the mother carries the same variant, she exhibits no clinical symptoms, suggesting incomplete penetrance. This variant is the first internationally reported instance. Its identification reinforces the central pathogenic role of TCOF1 in TCS, underscores the functional significance of the treacle protein's NLS, and expands variant databases. Penetrance variability complicates genetic counseling, necessitating future research into its genetic characteristics to enhance prenatal diagnostic accuracy.
Keywords: Treacher collins syndrome, TCOF1 gene, variant, Treacle protein, case report
Received: 21 Apr 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Zhang, Wang, Zhu, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yahong Liu, Lanzhou University Second Hospital, Lanzhou, China
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