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A. Ramirez–Miranda, G. Gascón–Guzmán, R. Velazquez–Montoya, J.C. Zenteno; Genotype–Phenotype Correlations in Mexican Patients With PAX6 Intragenic Deletions . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4629.
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© ARVO (1962-2015); The Authors (2016-present)
The PAX6 gene encodes a phylogenetically conserved transcriptional regulatory protein that is expressed in the developing eye, brain, spinal cord and pancreas. In humans, PAX6 is located in 11p13 and its mutations generate a spectrum of ocular phenotypes. Aniridia is a congenital ocular malformation that has an incidence of 1 in 40000 live births, and it is inherited in an autosomal dominant way with high penetrance. The most common PAX6 mutations associated with congenital aniridia are point mutations that generate the introduction of a premature stop codon, while the other ocular phenotypes are associated to missense mutations. In this study we report the molecular analysis of the PAX6 gene in 5 mexican cases (3 familial and 2 sporadic).
We studied a total of 9 affected individuals including 3 familial and two sporadic cases. All subjects underwent full ophthalmologic examination. Genomic DNA was extracted from peripheral blood, all 14 exons of the PAX6 gene were amplified by PCR, and sequenced with the Big Dye Terminator cycle sequencing kit. The mutant exons were ligated by means of a TA–ligation method into the TA cloning vector pGEM–T and subcloned into DH5α E. coli competent cells, allowing the individual analysis of both the mutant and the normal allele.
8 patients exhibited total bilateral aniridia and one patient bilateral coloboma of the iris. We did not identifiy ocular or extraocular associated anomalies in any individual. We detected 3 intragenic deletions in the PAX6 gene: a 15bp deletion in exon 10 in Family I (Patients 1,2,3), a 14bp deletion in exon 7 in patient 4, and a 4bp deletion in exon 8 in Family III (patients 5 and 6), Family IV (patients 7 and 8) and patient 9.
All three deletions caused a frame–shifting, which introduced premature stop codons.
This is the first study of the PAX6 gene in Mexican patients with congenital aniridia. PAX6 mutations identified in this study have not been reported in subjects with congenital aniridia.
Although the most common PAX6 defects are non–sense mutations we observed frame–shifting deletions in all our cases.
The three identified mutations caused bilateral aniridia in all patients we studied except in patient 7 which exhibited bilateral coloboma of the iris.
Although cases with the 4bp deletion were not related, they came from the same geographical area of the country suggesting a founder effect in the origin of this mutation.
A more numerous sample is required to define the PAX6 mutational spectrum in Mexican subjects with aniridia.
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