PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia

Thumbnail Image
Date
2018-03-28
Authors
Souzeau, Emmanuelle
Rudkin, Adam K
Dubowsky, Andrew
Casson, Robert J
Muecke, James S
Mancel, Erica
Whiting, Mark
Mills, Richard Arthur
Burdon, Kathryn Penelope
Craig, Jamie E
Journal Title
Journal ISSN
Volume Title
Publisher
Molecular Vision
Abstract
Purpose Aniridia is a congenital disorder caused by variants in the PAX6 gene. In this study, we assessed the involvement of PAX6 in patients with aniridia from Australasia and Southeast Asia. Methods Twenty-nine individuals with aniridia from 18 families originating from Australia, New Caledonia, Cambodia, Sri Lanka, and Bhutan were included. The PAX6 gene was investigated for sequence variants and analyzed for deletions with multiplex ligation-dependent probe amplification. Results We identified 11 sequence variants and six chromosomal deletions, including one in mosaic. Four deleterious sequence variants were novel: p.(Pro81HisfsTer12), p.(Gln274Ter), p.(Ile29Thr), and p.(Met1?). Ocular complications were associated with a progressive loss of visual function as shown by a visual acuity ≤ 1.00 logMAR reported in 65% of eyes. The prevalence of keratopathy was statistically significantly higher in the Australasian cohort (78.6%) compared with the Southeast Asian cohort (9.1%, p=0.002). Variants resulting in protein truncating codons displayed limited genotype–phenotype correlations compared with other variants. Conclusions PAX6 variants and deletions were identified in 94% of patients with aniridia from Australasia and Southeast Asia. This study is the first report of aniridia and variations in PAX6 in individuals from Cambodia, Sri Lanka, Bhutan, and New Caledonia, and the largest cohort from Australia.
Description
Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms)
Keywords
Aniridia, PAX6 gene, multiplex ligation-dependent probe amplification
Citation
Souzeau, E., Rudkin, A. K., Dubowsky, A., Casson, R. J., Muecke, J. S., Mancel, E., ... & Craig, J. E. (2018). PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia. Molecular Vision, 24, 261.