Purpose: To present the results of molecular analysis of the PAX6 gene in a group of patients with congenital aniridia from Mexican mestizo origin, a previously unstudied ethnic group.
Methods: Five unrelated affected probands, four pertaining to familial cases and one sporadic, were studied at the Institute of Ophthalmology "Conde de Valenciana" in Mexico City. All patients underwent full ophthalmologic examination as well as PAX6 analysis in genomic DNA using a combination of exon-by-exon PCR amplification, direct sequencing, and allele-specific cloning/sequencing. Available affected relatives were also investigated.
Results: Three novel intragenic deletions were identified: a 15 bp deletion in exon nine that removes the last two codons of the exon and the first nine bases of intron 10, including the conserved GT splicing donor signal; a 14 bp deletion in exon six that introduces a premature stop signal 15 codons downstream and a four bp deletion in exon seven, which introduces a stop signal 22 codons downstream, in three unrelated probands. Although unrelated, these three latter cases came from the same geographical area, strongly suggesting a founder mutation effect as the source of the anomaly.
Conclusions: Our study provides the first molecular analysis of the PAX6 gene in Mexican subjects with congenital aniridia, identifies three novel intragenic PAX6 deletions, and suggests the occurrence of a PAX6 founder mutation effect in this population. Our results also confirm the current notion that PAX6 truncating mutations are overwhelmingly associated with aniridia regardless of their location in the gene.