PAX6 allelic heterogeneity in Mexican congenital aniridia patients: expanding the mutational spectrum with seven novel pathogenic variants.

IMPORTANCE

The importance of the study was to describe the clinical characteristics and mutational analysis of Mexican patients with aniridia.

BACKGROUND

Aniridia is a panocular hereditary eye disease caused by mutations in the PAX6 transcription factor. Mutation detection rate is highly variable ranging from 30% to 90% in different populations. Very few studies have been published about the PAX6 mutational analysis in aniridia patients from Mexico. In order to establish a more representative PAX6 mutational frequency in the country, a cohort of 22 Mexican unrelated aniridia probands were analysed in this study.

DESIGN

Case series.

PARTICIPANTS

A total of 22 Mexican probands with bilateral isolated aniridia and their available relatives were included.

METHODS

Sanger sequencing was used for the mutational analysis of all coding exons and flanking intronic regions of PAX6.

MAIN OUTCOME MEASURES

Clinical characteristics and results of PAX6 mutational analysis in probands with aniridia and available family members.

RESULTS

Molecular analysis of PAX6 in 22 index cases with aniridia allowed the identification of a total of 16 different mutations. Seven of these pathogenic variants are novel, including c.183C>G, p.(Y61*); c.718delC, p.(R240Efs3); c.1149_1152delTCAG, p.(P385Wfs139); c.257_266delAAATAGCCCA, p.(K86Sfs35); c.836_843dupGCAACACA p.(P282Afs86); c.1032+2_1032+3insT; and c.141+2T>A. Inter and intrafamilial phenotypic heterogeneity was found.

CONCLUSIONS AND RELEVANCE

The mutational diagnostic rate in this series was 77%, which is comparable with reports from other populations. Importantly, no founder mutations were identified in this case series. Our results add 7 novel PAX6 pathogenic variants to the aniridia-related mutational spectrum and reveal considerable PAX6 allelic heterogeneity in this population.