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Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly.
Invest Ophthalmol Vis Sci. 2002 Dec; 43(12):3613-6.IO

Abstract

PURPOSE

To determine the possible molecular genetic defect underlying Axenfeld-Rieger anomaly (ARA) and to identify the pathogenic mutation causing this anterior segment dysgenesis in an Indian pedigree.

METHODS

The FOXC1 gene was amplified from genomic DNA of members of an ARA-affected family and control subjects using four novel sets of primers. The amplicons were directly sequenced, and the sequences were analyzed to identify the disease-causing mutation.

RESULTS

A heterozygous novel missense mutation was identified in the coding region of the FOXC1 gene in all three patients in this family. Consistent with the autosomal dominant inheritance pattern, the mutation segregated with the disease phenotype and was fully penetrant. The mutation was found in the wing region of the highly conserved forkhead domain of the FOXC1 gene and resulted in a very severe phenotype leading to blindness.

CONCLUSIONS

This is the first study to demonstrate that a mutation in the FOXC1 wing region can cause an anterior segment dysgenesis of the eye. This mutation resulted in blindness in the ARA-affected family, and the findings suggest that the FOXC1 wing region has a functional role in the normal development of the eye. Moreover, this is the first study from India to report the genetic etiology of Axenfeld-Rieger anomaly. Genotype-phenotype correlations of FOXC1 may help in establishing the disease prognosis and also in understanding the clinical and genetic heterogeneity associated with various anterior segment dysgenesis caused by this gene.

Authors+Show Affiliations

Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L. V. Prasad Eye Institute, India. shirly@lvpeye.stph.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12454026

Citation

Panicker, Shirly G., et al. "Novel Mutation in FOXC1 Wing Region Causing Axenfeld-Rieger Anomaly." Investigative Ophthalmology & Visual Science, vol. 43, no. 12, 2002, pp. 3613-6.
Panicker SG, Sampath S, Mandal AK, et al. Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly. Invest Ophthalmol Vis Sci. 2002;43(12):3613-6.
Panicker, S. G., Sampath, S., Mandal, A. K., Reddy, A. B., Ahmed, N., & Hasnain, S. E. (2002). Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly. Investigative Ophthalmology & Visual Science, 43(12), 3613-6.
Panicker SG, et al. Novel Mutation in FOXC1 Wing Region Causing Axenfeld-Rieger Anomaly. Invest Ophthalmol Vis Sci. 2002;43(12):3613-6. PubMed PMID: 12454026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly. AU - Panicker,Shirly G, AU - Sampath,Srirangan, AU - Mandal,Anil K, AU - Reddy,Aramati B M, AU - Ahmed,Niyaz, AU - Hasnain,Seyed E, PY - 2002/11/28/pubmed PY - 2002/12/13/medline PY - 2002/11/28/entrez SP - 3613 EP - 6 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 43 IS - 12 N2 - PURPOSE: To determine the possible molecular genetic defect underlying Axenfeld-Rieger anomaly (ARA) and to identify the pathogenic mutation causing this anterior segment dysgenesis in an Indian pedigree. METHODS: The FOXC1 gene was amplified from genomic DNA of members of an ARA-affected family and control subjects using four novel sets of primers. The amplicons were directly sequenced, and the sequences were analyzed to identify the disease-causing mutation. RESULTS: A heterozygous novel missense mutation was identified in the coding region of the FOXC1 gene in all three patients in this family. Consistent with the autosomal dominant inheritance pattern, the mutation segregated with the disease phenotype and was fully penetrant. The mutation was found in the wing region of the highly conserved forkhead domain of the FOXC1 gene and resulted in a very severe phenotype leading to blindness. CONCLUSIONS: This is the first study to demonstrate that a mutation in the FOXC1 wing region can cause an anterior segment dysgenesis of the eye. This mutation resulted in blindness in the ARA-affected family, and the findings suggest that the FOXC1 wing region has a functional role in the normal development of the eye. Moreover, this is the first study from India to report the genetic etiology of Axenfeld-Rieger anomaly. Genotype-phenotype correlations of FOXC1 may help in establishing the disease prognosis and also in understanding the clinical and genetic heterogeneity associated with various anterior segment dysgenesis caused by this gene. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/12454026/Novel_mutation_in_FOXC1_wing_region_causing_Axenfeld_Rieger_anomaly_ L2 - https://iovs.arvojournals.org/article.aspx?volume=43&issue=12&page=3613 DB - PRIME DP - Unbound Medicine ER -