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N. Fuse, K. Takahashi, S.–J. Yokokura, M. Tamai; Novel Mutations in FOXC1 Gene in Japanese Patients With Axenfeld–Rieger Syndrome . Invest. Ophthalmol. Vis. Sci. 2005;46(13):35.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mutations in the forkhead transcription factor gene (FOXC1) have been shown to cause some cases of juvenile glaucoma associated with a variety of anterior–segment anomalies. The purpose of this study was to report the ocular and genetic findings of two Japanese families with the Axenfeld–Rieger (AR) syndrome. Methods: Genomic DNA was extracted from the leukocytes of members in two families with the AR syndrome. The DNA from the exon of the FOXC1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. Results: Mutational screening and sequence analysis of the FOXC1 gene revealed a novel Ala85Pro missense mutation in Helix1 (family 1), and deletion of 17 nucleotides (437–453) in Wing1 and Beta2 (family 2) within the forkhead domain of the FOXC1 gene. This deletion predicted a loss of the forkhead domain by a premature termination of translation. The mutations segregated with the ARS phenotype in these families as autosomal dominant mutations. The affected individuals in family 1 had posterior embryotoxon, iris hypoplasia, corectopia with severe early–onset glaucoma, atrial septal defect, aortic stenosis, and pulmonary stenosis. The 5 affected individuals in family 2 had posterior embryotoxon and iris hypoplasia with early–onset glaucoma. The members in family 2 showed general features such as hearing loss, hypertelorism and telecanthus.Conclusions: A novel mutation in Helix1, and novel deletion in Wing1 and Beta2 of the forkhead domain of the FOXC1 gene have been identified confirming that mutations in the FOXC1 gene cause developmental abnormalies in the anterior segment of the eye.
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