Familial aniridia due to a regulatory PAX6 deletion
diagnostic challenges and the relevance of maternal mosaicism
DOI:
https://doi.org/10.70313/2718.7446.v18.n4.469Keywords:
aniridia, mosaicism, array CGH, PAX6Abstract
Objective: Aniridia is a rare panocular disorder. It is inherited in an autosomal dominant manner and in 90% of cases is caused by variants in PAX6 which can be single nucleotide variants, deletions affecting the entire gene, or the regulatory region 11p13, or comprise contiguous gene syndromes. Up to 30% percent of variants are de novo, and the rate of mosaicism could reach 17.5%. Our objective was to report and characterize a familial case of aniridia associated with a microdeletion in the regulatory region of PAX6, assessing its genotype–phenotype correlation and the contribution of maternal mosaicism to the clinical spectrum.
Case report: We present a 12-year-old patient with postnatal diagnosis of bilateral aniridia. A gene panel for ocular pathology that did not detect any variants relevant and an a-CGH (180k), which reported a 657 kb deletion in 11p13 comprising 4 OMIM genes linked to the regulatory region of PAX6. A-CGH study in the mother reported the same microdeletion in mosaic (20%), with nuclear cataract in the left eye and partial aniridia.
Conclusions: We describe a case of familial aniridia, with autosomal dominant inheritance, caused by deletion of the PAX6 gene regulatory region, with the mother exhibiting milder expression due to the deletion being a mosaic. Because of the clinical and genetic heterogeneity, and variable expression involved, we emphasize the importance of molecular analysis of patients combining different laboratory tools for adequate diagnosis and genetic counseling.
Downloads
References
1. Cheng F, Song W, Kang Y, Yu S, Yuan H. A 556 kb deletion in the downstream region of the PAX6 gene causes familial aniridia and other eye anomalies in a Chinese family. Mol Vis 2011; 17: 448-455.
2. Moosajee M, Hingorani M, Moore AT. PAX6-related aniridia. 2003 May 20 [updated 2018 Oct 18]. En: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [internet]. Seattle (WA): University of Washington, 1993-2025.
3. Li Y, Chen J, Zheng Y, Chen Z, Wang T, Sun Q, Wan X, Liu H, Sun X. A novel microdeletion of 517 kb downstream of the PAX6 gene in a Chinese family with congenital aniridia. BMC Ophthalmol 2023; 23(1): 393. doi: 10.1186/s12886-023-03147-1.
4. Lima Cunha D, Arno G, Corton M, Moosajee M. The spectrum of PAX6 mutations and genotype-henotype `correlations in the eye. Genes (Basel) 2019; 10(12): 1050. doi: 10.3390/genes10121050.
5. Wawrocka A, Krawczynski MR. The genetics of aniridia: simple things become complicated. J Appl Genet 2018; 59(2): 151-159. doi: 10.1007/s13353-017-0426-1.
6. Vasilyeva TA, Voskresenskaya AA, Käsmann-Kellner B, Khlebnikova OV, Pozdeyeva NA, Bayazutdinova GM, Kutsev SI, Ginter EK, Semina EV, Marakhonov AV, Zinchenko RA. Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations. Clin Genet 2017; 92(6): 639-644. doi: 10.1111/cge.13019.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Consejo Argentino de Oftalmología
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Con esta licencia no se permite un uso comercial de la obra original, ni la generación de obras derivadas. Las licencias Creative Commons permiten a los autores compartir y liberar sus obras en forma legal y segura.
How to Cite
