Mutational Analysis of FOXC1 and PITX2 Genes in Japanese Families With Axenfeld-Rieger Syndrome

Abstract

Purpose:: Axenfeld-Rieger Syndrome (ARS) is a hereditary disease characterized by developmental abnormality of the anterior segment, and is associated with mutations of the FOXC1 and PITX2 genes, which encode transcription factors that interact with each other. The aim of this study is to determine the clinical and genetic characteristics of Japanese patients with ARS

Methods:: Complete ophthalmologic examinations were performed and all exons of the PITX2 and FOXC1 were directly sequenced in 2 Japanese families with ARS.

Results:: (Family 1) 12- and 10-year-old Japanese brothers exhibited bilateral posterior embryotoxon and cord-like tissues in the angle. No systemic abnormality was found. A Gln23Stop mutation in FOXC1 was detected in both affected individuals. (Family 2) A 40-year-old proband and his 8-year-old daughter showed posterior embryotoxon and cord-like tissues bilaterally. Dental anomalies were observed in both patients. A 166delC mutation in PITX2 was detected.

Conclusions:: Our results confirmed the previous notion that ARS is caused by the two genes, and that the FOXC1 and PITX2 may play an important role in the development of the human anterior segment. ARS patients with non-ocular findings appear likely to have PITX2 rather than FOXC1 mutations.

Clinical Trial:: www.umin.ac.jp/ctr/index/htm ikoike-oph

Keywords: genetics • gene/expression • anterior segment