Molecular characterization of a rare TP63 variant associated with split-hand/split-foot malformation 4 and incomplete penetrance: disruption of the p63-Dlx signaling pathway
This study identifies, for the first time, the TP63 gene variant c.956G > A (p.Arg319His) as a causative factor for SHFM4 in Chinese individuals with incomplete penetrance. In addition, we hypothesize that the p.Arg319His variant functions as a gain-of-function variant, leading to the upregulation of cell adhesion target genes. Such upregulation then disrupts the p63-Dlx signaling pathway and causes AER stratification failure.
Authors
- Jianlong Zhuang (ORCID: https://orcid.org/0000-0001-8087-205X)
- Chunnuan Chen (ORCID: https://orcid.org/0000-0002-8906-3184)
- Manman Hu
- Hegan Zhang
- Shufen Liu (ORCID: https://orcid.org/0000-0002-0273-0213)
- Yanqing Li (ORCID: https://orcid.org/0000-0003-0575-0399)
- Yue Chen (ORCID: https://orcid.org/0000-0003-4863-0864)
Institutions
- Fujian Medical University (CN)
- Fujian Women and Children Hospital (CN)
- The 180th Hospital of PLA (CN)
- Second Affiliated Hospital of Fujian Medical University (CN)
- Berry Oncology (China) (CN)
Publication Details
- Journal
- BMC Genomics
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1186/s12864-025-11297-3
- Primary Topic
- Congenital limb and hand anomalies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Huaqiao University
- Science and Technology Bureau of Quanzhou