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

dc.contributor.author Souzeau, Emmanuelle
dc.contributor.author Rudkin, Adam K
dc.contributor.author Dubowsky, Andrew
dc.contributor.author Casson, Robert J
dc.contributor.author Muecke, James S
dc.contributor.author Mancel, Erica
dc.contributor.author Whiting, Mark
dc.contributor.author Mills, Richard Arthur
dc.contributor.author Burdon, Kathryn Penelope
dc.contributor.author Craig, Jamie E
dc.date.accessioned 2018-04-10T02:10:43Z
dc.date.available 2018-04-10T02:10:43Z
dc.date.issued 2018-03-28
dc.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) en_US
dc.description.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. en_US
dc.identifier.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. en_US
dc.identifier.issn 1090-0535
dc.identifier.uri http://hdl.handle.net/2328/37895
dc.language.iso en en_US
dc.publisher Molecular Vision en_US
dc.relation http://purl.org/au-research/grants/nhmrc/1023911 en_US
dc.relation http://purl.org/au-research/grants/nhmrc/1065433 en_US
dc.relation.grantnumber NHMRC/1023911 en_US
dc.relation.grantnumber NHMRC/1065433 en_US
dc.rights The authors retain copyright and grant Molecular Vision an irrevocable, royalty-free, perpetual license to publish and distribute the article, in all formats now known or later developed, and to identify Molecular Vision as the original publisher en_US
dc.rights.holder The authors en_US
dc.rights.license CC-BY-NC-ND
dc.subject Aniridia en_US
dc.subject PAX6 gene en_US
dc.subject multiplex ligation-dependent probe amplification en_US
dc.title PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia en_US
dc.type Article en
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