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Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-Rieger anomaly in India.
Mol Vis. 2003 Feb 18; 9:43-8.MV

Abstract

PURPOSE

Axenfeld-Rieger anomaly (ARA) is a form of anterior segment dysgenesis of the eye, mainly caused by mutations in the FOXC1 gene. We had earlier reported a novel mutation in the wing region of FOXC1 in an autosomal dominant family. The present study was aimed to identify the spectrum of mutations in the FOXC1 gene in a cohort of Indian ARA patients from different ethnic backgrounds, and to understand its role in the disease pathogenesis.

METHODS

Two new autosomal dominant families and seven sporadic cases of ARA from different ethnic backgrounds were screened for mutations by direct sequencing of the coding region of the FOXC1 gene. Another autosomal dominant ARA family that was previously reported by us was also included for comparative analysis of clinical genetic parameters. The segregation of the mutations in the autosomal dominant families was analyzed by haplotype and restriction analysis. Genotype-phenotype correlation were also undertaken to study the role of FOXC1 in phenotypic manifestation in the patient cohort.

RESULTS

Three of the nine ARA cases harbored mutations in FOXC1, of which two novel nonsense mutations Q2X and Q123X, resulted in haploinsufficiency of the gene product. The missense mutation (M161K) that we previously reported in an autosomal dominant family was also found in another family. Haplotype analysis of these two families suggested multiple founders in the same ethnic group. The mutations resulted in variable expressions of phenotype among the patients as assessed from their prognosis based on visual outcomes.

CONCLUSIONS

Significant genetic heterogeneity of FOXC1 was observed in a multi-ethnic population studied in this region of India resulting in variable ARA phenotypes. The different visual outcome seen in the patients suggest a variable expression of FOXC1 and also provide some insight for understanding the gene functions in this population.

Authors+Show Affiliations

Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, Hyderabad, India.No affiliation info availableNo 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

12592227

Citation

Komatireddy, Sreelatha, et al. "Mutation Spectrum of FOXC1 and Clinical Genetic Heterogeneity of Axenfeld-Rieger Anomaly in India." Molecular Vision, vol. 9, 2003, pp. 43-8.
Komatireddy S, Chakrabarti S, Mandal AK, et al. Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-Rieger anomaly in India. Mol Vis. 2003;9:43-8.
Komatireddy, S., Chakrabarti, S., Mandal, A. K., Reddy, A. B., Sampath, S., Panicker, S. G., & Balasubramanian, D. (2003). Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-Rieger anomaly in India. Molecular Vision, 9, 43-8.
Komatireddy S, et al. Mutation Spectrum of FOXC1 and Clinical Genetic Heterogeneity of Axenfeld-Rieger Anomaly in India. Mol Vis. 2003 Feb 18;9:43-8. PubMed PMID: 12592227.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-Rieger anomaly in India. AU - Komatireddy,Sreelatha, AU - Chakrabarti,Subhabrata, AU - Mandal,Anil Kumar, AU - Reddy,Aramati Bindu Madhava, AU - Sampath,Srirangan, AU - Panicker,Shirly George, AU - Balasubramanian,Dorairajan, Y1 - 2003/02/18/ PY - 2003/2/20/pubmed PY - 2003/2/26/medline PY - 2003/2/20/entrez SP - 43 EP - 8 JF - Molecular vision JO - Mol Vis VL - 9 N2 - PURPOSE: Axenfeld-Rieger anomaly (ARA) is a form of anterior segment dysgenesis of the eye, mainly caused by mutations in the FOXC1 gene. We had earlier reported a novel mutation in the wing region of FOXC1 in an autosomal dominant family. The present study was aimed to identify the spectrum of mutations in the FOXC1 gene in a cohort of Indian ARA patients from different ethnic backgrounds, and to understand its role in the disease pathogenesis. METHODS: Two new autosomal dominant families and seven sporadic cases of ARA from different ethnic backgrounds were screened for mutations by direct sequencing of the coding region of the FOXC1 gene. Another autosomal dominant ARA family that was previously reported by us was also included for comparative analysis of clinical genetic parameters. The segregation of the mutations in the autosomal dominant families was analyzed by haplotype and restriction analysis. Genotype-phenotype correlation were also undertaken to study the role of FOXC1 in phenotypic manifestation in the patient cohort. RESULTS: Three of the nine ARA cases harbored mutations in FOXC1, of which two novel nonsense mutations Q2X and Q123X, resulted in haploinsufficiency of the gene product. The missense mutation (M161K) that we previously reported in an autosomal dominant family was also found in another family. Haplotype analysis of these two families suggested multiple founders in the same ethnic group. The mutations resulted in variable expressions of phenotype among the patients as assessed from their prognosis based on visual outcomes. CONCLUSIONS: Significant genetic heterogeneity of FOXC1 was observed in a multi-ethnic population studied in this region of India resulting in variable ARA phenotypes. The different visual outcome seen in the patients suggest a variable expression of FOXC1 and also provide some insight for understanding the gene functions in this population. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/12592227/Mutation_spectrum_of_FOXC1_and_clinical_genetic_heterogeneity_of_Axenfeld_Rieger_anomaly_in_India_ L2 - http://www.molvis.org/molvis/v9/a7/ DB - PRIME DP - Unbound Medicine ER -