title: Current molecular understanding of Axenfeld-Rieger syndrome.
abstract: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant inherited disorder affecting the development of the eyes, teeth and abdomen. The syndrome is characterised by complete penetrance but variable expressivity. The ocular component of the ARS phenotype has acquired most clinical attention and has been dissected into a spectrum of developmental eye disorders, of which open-angle glaucoma represents the main challenge in terms of treatment. Mutations in several chromosomal loci have been implicated in ARS, including PITX2, FOXC1 and PAX6. Full-spectrum ARS is caused primarily by mutations in the PITX2 gene. The homeobox transcription factor PITX2 is produced as at least four different transcriptional and splicing isoforms, with different biological properties. Intriguingly, PITX2 is also involved in left-right polarity determination, although asymmetry defects are not a feature of ARS. In experimental animal models and in cell culture experiments using PITX2, abundant evidence indicates that a narrow window of expression level of this gene is vital for its correct function.
authors.affiliation: Lund University, Department of Experimental Medical Research, BMC B12, Tornavägen 10, SE-22184 Lund, Sweden. tord.hjalt@med.lu.se
authors.forename: Tord A
authors.initials: TA
authors.lastname: Hjalt
authors.forename: Elena V
authors.initials: EV
authors.lastname: Semina
mesh_terms: D000005:Abdomen / Q000002:abnormalities*; D000818:Animals; D005124:Eye Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2