3.4. Discovery of new PAH gene mutations
Three missense mutations of the PAH gene (p.a47e, p.i65s and p.a259t; Figure 2), were found for the first time in the Chinese population. By comparing information held in the PAH database, Human Gene Mutation Database, and ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), we identified three previously unreported PAH gene mutations (p.c334x, p.g46d, and p.g256d; Figure 3). Among them, p.c334x (c.1002c>a) is a TGC mutation of the Cys codon on exon 10, resulting in the early termination of protein translation, leading to the loss of the partial catalytic and C-terminal tetramer regions, thereby generating a protein that is unable to a form a tetramer and lacking catalytic activity.