Human Molecular Genetics, 2002, Vol. 11, No. 10 1177-1187
© 2002 Oxford University Press
Molecular genetics of Axenfeld–Rieger malformations
1Ocular Genetics Laboratory, Department of Ophthalmology, 8-32 Medical Sciences Building, University of Alberta, Edmonton, Canada T6G 2E1
Received February 15, 2002; Accepted February 22, 2002
Axenfeld–Rieger (AR) malformations are autosomal dominant developmental defects of the anterior segment of the eye, and often result in glaucomatous blindness. AR malformations are associated with mutations in two transcription factor genes (PITX2 and FOXC1) expressed throughout eye ontogeny. Studies of disease-associated mutant proteins have provided insights into the aetiology of AR malformations, while delineating residues and domains important to DNA binding, transactivation and nuclear localization. The availability of mouse models for both PITX2 and FOXC1 has allowed detailed study of their expression and mutant phenotypes. Dissection of the normal functions and domain structures of these factors will aid in future elucidation of how alterations of the developmental program produce the dysgenic phenotypes seen in AR. There are at least two AR loci still awaiting molecular cloning on chromosomes 13q14 and 16q24. Identification of further genes implicated in aberrations of human ocular development will advance our understanding of the mechanisms whereby pattern is established in the eye, and may be of clinical value in treating the glaucoma that is the most serious consequence of AR malformations.
* To whom correspondence should be addressed. Tel: +1 780 492 7557; Fax: +1 780 492 6934; Email: mwalter{at}ualberta.ca
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