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Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome.
Mol Vis. 2007 Jun 27; 13:1005-9.MV

Abstract

PURPOSE

Mutations in the forkhead transcription factor (FOXC1) gene have been shown to cause juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to determine the ocular and genetic characteristics of two Japanese families with Axenfeld-Rieger syndrome (ARS).

METHODS

Genomic DNA was extracted from the leukocytes of six members of two families with ARS. The DNA from one exon of the FOXC1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The patients received standard systemic and ophthalmological examinations.

RESULTS

Sequence analysis of the FOXC1 gene revealed a novel Ala85Pro missense mutation in Helix1 in family 1 and a deletion of 17 nucleotides (437-453) in Wing1 and Beta2 within the forkhead domain of the FOXC1 gene in family 2. This deletion predicted a loss of the forkhead domain by a premature termination of translation. These mutations segregated with the ARS phenotype in an autosomal dominant pattern. The affected individuals in family 1 had posterior embryotoxon, iris hypoplasia, corectopia with early-onset severe glaucoma, atrial septal defect, aortic stenosis, and pulmonary stenosis. The affected members in family 2 had posterior embryotoxon and iris hypoplasia with early-onset glaucoma, and systemically they had hearing loss, hypertelorism, and telecanthus.

CONCLUSIONS

A novel mutation in Helix1 and a novel deletion in Wing1 and Beta2 of the forkhead domain of the FOXC1 gene have been identified in two families with ARS. FOXC1 mutations cause a variety of developmental abnormalities in the anterior segment of the eye, and they also induce an elevation in intraocular pressures and early-onset glaucoma.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. fusen@oph.med.tohoku.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17653043

Citation

Fuse, Nobuo, et al. "Novel Mutations in the FOXC1 Gene in Japanese Patients With Axenfeld-Rieger Syndrome." Molecular Vision, vol. 13, 2007, pp. 1005-9.
Fuse N, Takahashi K, Yokokura S, et al. Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome. Mol Vis. 2007;13:1005-9.
Fuse, N., Takahashi, K., Yokokura, S., & Nishida, K. (2007). Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome. Molecular Vision, 13, 1005-9.
Fuse N, et al. Novel Mutations in the FOXC1 Gene in Japanese Patients With Axenfeld-Rieger Syndrome. Mol Vis. 2007 Jun 27;13:1005-9. PubMed PMID: 17653043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome. AU - Fuse,Nobuo, AU - Takahashi,Kana, AU - Yokokura,Shunji, AU - Nishida,Kohji, Y1 - 2007/06/27/ PY - 2007/7/27/pubmed PY - 2007/9/5/medline PY - 2007/7/27/entrez SP - 1005 EP - 9 JF - Molecular vision JO - Mol Vis VL - 13 N2 - PURPOSE: Mutations in the forkhead transcription factor (FOXC1) gene have been shown to cause juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to determine the ocular and genetic characteristics of two Japanese families with Axenfeld-Rieger syndrome (ARS). METHODS: Genomic DNA was extracted from the leukocytes of six members of two families with ARS. The DNA from one exon of the FOXC1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The patients received standard systemic and ophthalmological examinations. RESULTS: Sequence analysis of the FOXC1 gene revealed a novel Ala85Pro missense mutation in Helix1 in family 1 and a deletion of 17 nucleotides (437-453) in Wing1 and Beta2 within the forkhead domain of the FOXC1 gene in family 2. This deletion predicted a loss of the forkhead domain by a premature termination of translation. These mutations segregated with the ARS phenotype in an autosomal dominant pattern. The affected individuals in family 1 had posterior embryotoxon, iris hypoplasia, corectopia with early-onset severe glaucoma, atrial septal defect, aortic stenosis, and pulmonary stenosis. The affected members in family 2 had posterior embryotoxon and iris hypoplasia with early-onset glaucoma, and systemically they had hearing loss, hypertelorism, and telecanthus. CONCLUSIONS: A novel mutation in Helix1 and a novel deletion in Wing1 and Beta2 of the forkhead domain of the FOXC1 gene have been identified in two families with ARS. FOXC1 mutations cause a variety of developmental abnormalities in the anterior segment of the eye, and they also induce an elevation in intraocular pressures and early-onset glaucoma. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/17653043/Novel_mutations_in_the_FOXC1_gene_in_Japanese_patients_with_Axenfeld_Rieger_syndrome_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/17653043/ DB - PRIME DP - Unbound Medicine ER -