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J.P. Vasconcellos, M.B. Melo, W.P. Cella, B. Kneipp, M.N. Rocha, F. Richeti, C.A. Longui, V.P. Costa; Mutation Screening of FOXC1 and PITX2 Genes in Brazilian Patients With Axenfeld–Rieger Malformations . Invest. Ophthalmol. Vis. Sci. 2005;46(13):45.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Axenfeld–Rieger (AR) malformation is a rare disorder, usually transmitted in an autosomal dominant pattern, characterized by anterior segment dysgenesis and often associated with developmental glaucoma. Besides the ocular changes observed in AR malformations, syndromic features can also occur such as facial bone defects, teeth anomalies and periumbilical skin involution. Two transcription factor genes PITX2 gene , on chromosome 4q25 and FOXC1 gene, on chromosome 6p25, have been associated with AR malformation phenotype. The purpose of this study was to evaluate FOXC1 and PITX2 gene mutations in Brazilian patients with AR malformations. Methods: Eight unrelated patients affected by AR malformations (all of them with glaucoma and 5 without systemic malformations) and their families were ophthalmologically evaluated and had their blood collected for DNA extraction purposes. The coding regions of these genes were completely evaluated through direct sequencing. Results: Among the 8 patients, 3 (37,5%) presented with different structural alterations in the FOXC1 gene. A deletion, in heterozygosis, of two bases at positions 718–719 downstream of the forkhead domain was observed in a patient with no systemic malformations (718–719delCT). An insertion of three bases at position 1359, also downstream of the forkhead domain, leading to the addition of the aminoacid Gly was identified in a patient with systemic malformation (1359–1360insGGC). A new nonsense mutation (Trp152STOP) was identified in the forkhead domain of the FOXC1 gene in another patient with AR malformations and systemic alterations as well. No mutations were identified in the PITX2 gene among these individuals. Conclusions: Three new structural alterations of the FOXC1 gene were described in Brazilian patients with AR malformations, totalizing 37,5% of the patients evaluated. This is the first description of FOXC1 gene mutations in Brazilian patients involving AR malformations with and without systemic alterations.
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