Two Novel Mutations of PITX2 in Patients With Axenfeld–Rieger Syndrome

Objectives: The purpose of this study was to explore two new nonsense PITX2 mutations and the other one missense PITX2 mutation, and to investigate the functional impact of the mutant PITX2A proteins.
Methods: These individuals’ and their famliy members’ DNA samples were prepared from their peripheral blood or saliva, and then subjected to DNA sequencing and analysed. In silico secondary structure analysis was performed.
Results: we identified two novel nonsense mutations of PITX2 gene (NM_153427,c.148C>T,p.Q50X; NM_153427,c.257G>A,p.W86X) .And we also identified one missense mutation reported before (NM_153427,c.127C>T,p.R43W) in one patient with high throughput sequencing of other 40 congenital tooth agenesis patients. Fluorescence detection showed that these three mutant PITX2A proteins could still accumulate in the nucleus. But luciferase assay indicated all mutants severely impaired the transactivation activities of PITX2 on DLX2 promoter.
Conclusions: our results identified that these three mutations could impact the function of PITX2 and broadened the spectrum of PITX2 mutations in ARS individuals.