Novel variants of TP63 identified in Chinese families with split-hand/foot malformation
Objective Split-hand/foot malformation (SHFM) is a group of congenital birth defects affecting the hands and feet, significantly impairing patients quality of life. The TP63 gene encodes the p63 protein, heterozygous TP63 variants can cause SHFM. The aim of this study was to identify TP63 gene variants in three Chinese families with SHFM. Methods Three Chinese families with SHFM enrolled in this study. Proband 1 and Proband two had familial history of SHFM, whereas Proband 3 was a sporadic case of this disease. Peripheral blood was collected from the proband and their available family members for genomic DNA extraction. Candidate pathogenic variants were identified through whole exome sequencing (WES), validated using PCR-based Sanger sequencing and bioinformatic analysis. Results We found three different missense variants in the TP63 gene: c.2032G>C (p.Glu678Gln), c.956G>A (p.Arg319His), and c.689T>A (p.Val230Asp). Among them, c.689T>A (p.Val230Asp) is novel variant. Conclusion In the present work, three TP63 gene variants were found in the families with SHFM, which expanded the variant spectrum of TP63. These findings not only provide further evidence for their heterogeneous role in limb and non-limb malformations but also broaden the genetic spectrum of associated disorders. These insights pave the way for improved prenatal genetic diagnosis and informed counseling.