De Novo Missense Variant in TP63 Gene: Insights on Clinical and Molecular Investigations

This study aims to investigate the phenotypes, mutation types, and loci associated with TP63-related syndrome by focusing on an affected proband.

Employing a proband collection strategy, we identified a family presenting with TP63-related syndrome and performed thorough clinical evaluations on the proband and family members. We subsequently documented the phenotype, mutation type, and locus of the TP63 gene, followed by Sanger DNA sequencing analysis.

We identified a family affected by TP63-related syndrome. The proband, a young adult male, demonstrated congenital anodontia, hypohidrosis, sparse hair, and additional features characteristic of ectodermal dysplasia. Further clinical manifestations included left ear hearing impairment, cleft lip/palate, hypospadias, and syndactyly. Sequencing analysis revealed a missense nucleotide variant (c.184G>C, p.Val62Leu) in exon 2 of the TP63 gene. This variant was absent from established SNP databases and was not detected in other family members or unrelated healthy individuals.

The family exhibits significant symptoms consistent with TP63 syndrome. The identified missense mutation is preliminarily considered to be pathogenic.