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N. Weisschuh, C. Wolf, B. Wissinger, E. Gramer; A Novel Mutation in the FOXC1 Gene in a Family With Axenfeld Rieger Syndrome and Peters Anomaly. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3119.
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Peters anomaly and Axenfeld Rieger Syndrome (ARS) are two rare forms of anterior segment dysgenesis. Because of the considerable phenotypic overlap between ARS and Peters anomaly and the occasional occurrence in different individuals of the same family, ARS and Peters anomaly are discussed to be part of the single disease spectrum of anterior segment dysgenesis. Five affected members of a family presenting with ARS with one member showing Peters anomaly were screened for mutations in PITX2, CYP1B1 and FOXC1.
Ophthalmic examination included slit lamp biomicroscopy and gonioscopy. In some cases, clinical data were obtained from the referring specialists. Patient DNA was extracted from peripheral blood lymphocytes using a standard salting-out procedure. Individual exons of the PITX2 and CYP1B1 gene were amplified by polymerase chain reaction (PCR) using appropriate amplification protocols. Amplification of the single FOXC1 exon was performed with a set of four overlapping primers. Sequencing was performed using Big Dye Termination chemistry.
Clinical examination showed that the five affected family members demonstrate a substantial degree of intrafamilial phenotypic variability. Whereas all patients show iris hypoplasia and iris processes, other findings like corectopia, maxillary hypoplasia, ocular hypertelorism, umbilicus or atrial septal defect are limited to individual members. One patient showed bilateral central corneal opacities with peripheral vascularization and adhesion between the cornea and the iridic-pupillary border consistent with Peters Anomaly.While no disease-causing mutations could be detected in PITX2 or CYP1B1, sequencing analysis of the FOXC1 coding sequence revealed a C>T transition at cDNA position 358 in all five affected members. This nucleotide change is predicted to change a glutamine residue to a premature stop codon at position 120 of the polypeptide (Q120X), causing a truncation of the FOXC1 protein between helices 3 and 4 of the forkhead domain.
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