title: Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil.
abstract: OBJECTIVE
  Axenfeld-Rieger syndrome is a genetically heterogeneous, autosomal dominant disorder that is characterized by anterior segment defects, glaucoma, and extraocular anomalies. This study examined the two genes known to cause Rieger syndrome, PITX2 and FOXC1, for mutations in five Brazilian families with Axenfeld-Rieger syndrome.
  
  
  METHODS
  Five families with a total of 23 persons affected by Axenfeld-Rieger syndrome were recruited for this study. A sequencing-based mutation screen was undertaken for the PITX2 and FOXC1 genes. Linkage analysis was used to study one large family for which no mutations were detected in the PITX2 or FOXC1 genes.
  
  
  RESULTS
  Two of the five families harbored mutations in the PITX2 gene, but none of the families had a detectable FOXC1 mutation. Haplotypic analysis of three Rieger syndrome regions in a large family with Axenfeld-Rieger syndrome excluded linkage to the 4q25 (PITX2), 6p25 (FOXC1), and 13q14 (RIEG2) regions.
  
  
  CONCLUSIONS
  It appears that the PITX2 gene is responsible for a significant portion of Axenfeld-Rieger syndrome in the Brazilian population. Furthermore, there is also evidence for the presence of genetic heterogeneity of the disorder within the Brazilian population. Finally, a large family with Axenfeld-Rieger syndrome has been identified that does not appear to harbor any of the three known loci. Axenfeld-Rieger syndrome gene segregation in this family likely represents a novel locus.
authors.affiliation: Department of Ophthalmology and Otorrinolaryngology, Glaucoma Service University of São Paulo, São Paulo, Brazil.
authors.forename: Adriana Silva
authors.initials: AS
authors.lastname: Borges
authors.forename: Remo
authors.initials: R
authors.lastname: Susanna
authors.forename: José Carlos Eudes
authors.initials: JC
authors.lastname: Carani
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Betinjane
authors.forename: Wallace L
authors.initials: WL
authors.lastname: Alward
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Nishimura
mesh_terms: D001938:Brazil / Q000453:epidemiology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003315:Cornea / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005124:Eye Abnormalities / Q000208:ethnology / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D008040:Genetic Linkage; D005838:Genotype; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C112743:FOXC1 protein, human