PAX6 gene intragenic deletions in Mexican patients withcongenital aniridia

[摘要] Purpose: To present the results of molecular analysis of thePAX6 gene in a group of patients with congenital aniridia fromMexican mestizo origin, a previously unstudied ethnic group.Methods: Five unrelated affected probands, four pertaining tofamilial cases and one sporadic, were studied at the Institute ofOphthalmology "Conde de Valenciana" in Mexico City. All patientsunderwent full ophthalmologic examination as well as PAX6 analysisin genomic DNA using a combination of exon-by-exon PCR amplification,direct sequencing, and allele-specific cloning/sequencing. Availableaffected relatives were also investigated.Results: Three novel intragenic deletions were identified: a 15 bpdeletion in exon nine that removes the last two codons of the exon andthe first nine bases of intron 10, including the conserved GT splicingdonor signal; a 14 bp deletion in exon six that introduces a prematurestop signal 15 codons downstream and a four bp deletion in exon seven,which introduces a stop signal 22 codons downstream, in three unrelatedprobands. Although unrelated, these three latter cases came from thesame geographical area, strongly suggesting a founder mutation effect asthe source of the anomaly.Conclusions: Our study provides the first molecular analysis of thePAX6 gene in Mexican subjects with congenital aniridia, identifiesthree novel intragenic PAX6 deletions, and suggests the occurrenceof a PAX6 founder mutation effect in this population. Our resultsalso confirm the current notion that PAX6 truncating mutations areoverwhelmingly associated with aniridia regardless of their location inthe gene.

[学科分类] 生物化学/生物物理