PLOD1 and Axenfeld-Rieger syndrome: In this study, functional analyses demonstrated that the mutation identified in patients with ECD and ARS abolished the transcriptional activation of ANF- or PLOD1-driven luciferase reporter by PITX2 and eliminated the transcriptionally synergistic activation between PITX2 and NKX2.5, indicating that functionally impaired PITX2 is potentially an alternative molecular mechanism underpinning CHD and ARS.