Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil.
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.
Borges
Adriana Silva
AS
Department of Ophthalmology and Otorrinolaryngology, Glaucoma Service University of São Paulo, São Paulo, Brazil.
Susanna
Remo
R
Carani
José Carlos Eudes
JC
Betinjane
Alberto J
AJ
Alward
Wallace L
WL
Stone
Edwin M
EM
Sheffield
Val C
VC
Nishimura
Darryl Y
DY
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
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