title: Molecular genetics of Axenfeld-Rieger malformations.
abstract: 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.
authors.affiliation: Ocular Genetics Laboratory, Department of Ophthalmology, 8-32 Medical Sciences Building, University of Alberta, Edmonton, Canada T6G 2E1.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lines
authors.forename: Kathy
authors.initials: K
authors.lastname: Kozlowski
authors.forename: Michael A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000196:embryology; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009432:Neural Crest / Q000196:embryology; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C112743:FOXC1 protein, human; C112890:Foxc1 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse