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A. Ramirez-Miranda, M. Matias-Florentino, R. D. Wammanda, H. W. Idris, J. C. Zenteno; Congenital Aniridia With Unusual Associated Anomalies: Clinical Description and PAX6 Molecular Screening in Two Families. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1310. doi: https://doi.org/.
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PAX6 is a phylogenetically conserved transcription factor almost universally employed to direct eye development that regulates the tissue-specific expression of diverse molecules, including transcription factors, cell adhesion molecules, hormones, and structural proteins. Its mutations, frequently point mutations that generate the introduction of a premature stop codon, lead to a variety of hereditary ocular malformations being the most common congenital aniridia. Congenital aniridia has an incidence of 1 in 40000 live births and is inherited in an autosomal dominant way with high penetrance. Associated ocular anomalies can include congenital cataract, lens subluxation, glaucoma, and coloboma of retina and optic nerve.In this study we report the molecular screening of the PAX6 gene in a Mexican and a Nigerian familial case with congenital aniridia associated to uncommon eye anomalies.
Total genomic DNA was isolated from peripheral blood of two unrelated pedigrees: Family 1 is a two generation (two affected members) Mexican family with congenital aniridia associated with star-shaped cataract; family 2 is a three generation (four affected members) Nigerian family clinically diagnosed with aniridia associated with congenital ptosis. The coding exons of the human PAX6 gene were amplified by PCR and direct automated sequencing was performed.
Sequencing analysis of the coding region and exon/intron junctions of PAX6 in members of family 1 failed to detect any deleterious mutation. The sequencing results revealed a novel PAX6 nonsense mutation in one family: c.120C>A, which predicts a C40X in the protein reported for the first time in the Nigeria population.
This is the first study of the PAX6 gene in Nigerian patients with congenital aniridia. A PAX6 mutation identified in this study has already been reported in subjects with congenital aniridia. The identified mutation caused bilateral aniridia with the unusual association of congenital ptosis. Although the entire PAX6 sequence in family 1 was analyzed, no mutations were detected. We speculate that the probable source for this peculiar aniridia phenotype associated with a star- shaped cataract are mutations in remote 3' regulatory elements required for initiation of PAX6 expression. A more numerous sample is required to define the PAX6 mutational spectrum in Nigerian subjects with aniridia.
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