Tags

Type your tag names separated by a space and hit enter

Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma.
Invest Ophthalmol Vis Sci. 2006 May; 47(5):1803-9.IO

Abstract

PURPOSE

Axenfeld-Rieger (AR) is an autosomal dominant disorder with phenotypic heterogeneity characterized by anterior segment dysgenesis, facial bone defects, and redundant periumbilical skin. The PITX2 gene, on chromosome 4q25, and the FOXC1 gene, on chromosome 6p25, have been implicated in the different phenotypes of the syndrome through mutational events. Recently, the CYP1B1 gene was found to be associated with Peters' anomaly, and the gene associated with oculodentodigital dysplasia syndrome, which presents some similarities with AR, was identified (connexin 43--GJA1 gene). The purpose of this study was to evaluate PITX2, FOXC1, CYP1B1, and GJA1 gene mutations in Brazilian families with AR.

METHODS

Eight unrelated patients affected by AR (all eight with glaucoma and three with systemic manifestations) and their families were ophthalmologically evaluated and their blood was collected for DNA extraction purposes. The coding regions of PITX2, FOXC1, CYP1B1, and GJA1 genes were completely evaluated through direct sequencing.

RESULTS

The frequency of mutations in the FOXC1, GJA1, PITX2, and CYP1B1 genes in this study were 25%, 12.5%, 0% and 0%, respectively. In the FOXC1 gene, two GGC triplet insertions (GGC375ins and GGC447ins) defined as a polymorphism, and two new mutations--a deletion (718 to 719delCT) and a nonsense mutation (Trp152STOP)--were identified. One polymorphism (Ala253Val) was identified in the GJA1 gene in the same family presenting the Trp152STOP mutation in the FOXC1 gene. In this family harboring both structural alterations, two patients who carried the GJA1 (Ala253Val) and FOXC1 (Trp152STOP) mutations developed less severe glaucoma compared with family members presenting the FOXC1 (Trp152STOP) mutation alone.

CONCLUSIONS

Two new structural alterations in the FOXC1 gene and a polymorphism in the GJA1 gene were first described in Brazilian patients with AR and developmental glaucoma. A polymorphism in the GJA1 gene (Ala253Val), for the first time identified in association with AR, raises the possibility of its participation as a modifier gene.

Authors+Show Affiliations

Department of Ophthalmology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. wenercella@ig.com.brNo 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

16638984

Citation

Cella, Wener, et al. "Structural Assessment of PITX2, FOXC1, CYP1B1, and GJA1 Genes in Patients With Axenfeld-Rieger Syndrome With Developmental Glaucoma." Investigative Ophthalmology & Visual Science, vol. 47, no. 5, 2006, pp. 1803-9.
Cella W, de Vasconcellos JP, de Melo MB, et al. Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma. Invest Ophthalmol Vis Sci. 2006;47(5):1803-9.
Cella, W., de Vasconcellos, J. P., de Melo, M. B., Kneipp, B., Costa, F. F., Longui, C. A., & Costa, V. P. (2006). Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma. Investigative Ophthalmology & Visual Science, 47(5), 1803-9.
Cella W, et al. Structural Assessment of PITX2, FOXC1, CYP1B1, and GJA1 Genes in Patients With Axenfeld-Rieger Syndrome With Developmental Glaucoma. Invest Ophthalmol Vis Sci. 2006;47(5):1803-9. PubMed PMID: 16638984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma. AU - Cella,Wener, AU - de Vasconcellos,José Paulo Cabral, AU - de Melo,Mônica Barbosa, AU - Kneipp,Bianca, AU - Costa,Fernando Ferreira, AU - Longui,Carlos Alberto, AU - Costa,Vital Paulino, PY - 2006/4/28/pubmed PY - 2006/6/7/medline PY - 2006/4/28/entrez SP - 1803 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 47 IS - 5 N2 - PURPOSE: Axenfeld-Rieger (AR) is an autosomal dominant disorder with phenotypic heterogeneity characterized by anterior segment dysgenesis, facial bone defects, and redundant periumbilical skin. The PITX2 gene, on chromosome 4q25, and the FOXC1 gene, on chromosome 6p25, have been implicated in the different phenotypes of the syndrome through mutational events. Recently, the CYP1B1 gene was found to be associated with Peters' anomaly, and the gene associated with oculodentodigital dysplasia syndrome, which presents some similarities with AR, was identified (connexin 43--GJA1 gene). The purpose of this study was to evaluate PITX2, FOXC1, CYP1B1, and GJA1 gene mutations in Brazilian families with AR. METHODS: Eight unrelated patients affected by AR (all eight with glaucoma and three with systemic manifestations) and their families were ophthalmologically evaluated and their blood was collected for DNA extraction purposes. The coding regions of PITX2, FOXC1, CYP1B1, and GJA1 genes were completely evaluated through direct sequencing. RESULTS: The frequency of mutations in the FOXC1, GJA1, PITX2, and CYP1B1 genes in this study were 25%, 12.5%, 0% and 0%, respectively. In the FOXC1 gene, two GGC triplet insertions (GGC375ins and GGC447ins) defined as a polymorphism, and two new mutations--a deletion (718 to 719delCT) and a nonsense mutation (Trp152STOP)--were identified. One polymorphism (Ala253Val) was identified in the GJA1 gene in the same family presenting the Trp152STOP mutation in the FOXC1 gene. In this family harboring both structural alterations, two patients who carried the GJA1 (Ala253Val) and FOXC1 (Trp152STOP) mutations developed less severe glaucoma compared with family members presenting the FOXC1 (Trp152STOP) mutation alone. CONCLUSIONS: Two new structural alterations in the FOXC1 gene and a polymorphism in the GJA1 gene were first described in Brazilian patients with AR and developmental glaucoma. A polymorphism in the GJA1 gene (Ala253Val), for the first time identified in association with AR, raises the possibility of its participation as a modifier gene. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/16638984/Structural_assessment_of_PITX2_FOXC1_CYP1B1_and_GJA1_genes_in_patients_with_Axenfeld_Rieger_syndrome_with_developmental_glaucoma_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.05-0979 DB - PRIME DP - Unbound Medicine ER -