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K. Linkroum, T. Desronvil, E. DelBono, J. L. Wiggs; Differentiation of Phenotypes Associated With Genetic Defects Found in Three Known Anterior Segment Dysgenesis Genes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):891.
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© ARVO (1962-2015); The Authors (2016-present)
Three genes, FOXC1, PITX2 and PAX6 have been associated with anterior segment dysgenesis and early onset glaucoma. In these patients, anterior segment dysgenesis is defined as a broad spectrum of disease ranging from simple iris atrophy to severe Peter’s Anomaly. Specific phenotypic features associated with each gene have not been well defined. The purpose of this study is to determine the frequency of mutation in these genes in a cohort of patients with anterior segment dysgenesis and to determine if specific phenotypic features are associated with a particular gene.
Members of 31 families (55 total individuals) and 18 isolate patients were diagnosed with anterior segment dysgenesis after a complete ocular exam. A minimal phenotype was defined as iris atrophy. 75% of the patients evaluated also had glaucoma defined as an IOP greater than 22 without medications and optic nerve changes consistent with glaucomatous disease. Genomic DNA from the family probands and the isolate patients (49 total individuals) were screened in FOXC1, PITX2, and PAX6. For each gene, the entire coding sequence and flanking intron regions were amplified by PCR and sequenced directly on an automated ABI 3100 sequencer using BIGDYE chemistries and analyzed using Vector NTI software.
Mutations in FOXC1 were found in 7 patients (1 nonsense, 3 missense, 1 insertion, 1 deletion, and 1 insertion/deletion); mutations in PITX2 in 2 patients (2 nonsense), and a PAX6 missense mutation was found in 1 patient. All of the patients with FOXC1 mutations had iris atrophy as a phenotypic feature, and did not have dental or umbilicus abnormalities. PITX2 patients had dental abnormalities in addition to iris atrophy and other features of anterior segment dysgenesis. The patient with the PAX6 mutation had agenesis of the iris consistent with a diagnosis of aniridia. A correlation between gene mutation and glaucoma was not observed.
20% of the patients in this study with varying degrees of anterior segment dysgenesis were found to have a mutation in either FOXC1, PITX2 or PAX6. Dental abnormalities were found only in the PITX2 patients suggesting that this gene should be screened first in patients presenting with these findings.
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