Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation

Syrimis,Andreas; Nicolaou,Nayia; Alexandrou,Angelos; Papaevripidou,Ioannis; Nicolaou,Michael; Loukianou,Eleni; Sismani,Carolina; Malas,Stavros; Christophidou‑Anastasiadou,Violetta; Tanteles,George  A.

doi:10.3892/mmr.2018.9126

Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation

Authors:
- Andreas Syrimis
- Nayia Nicolaou
- Angelos Alexandrou
- Ioannis Papaevripidou
- Michael Nicolaou
- Eleni Loukianou
- Carolina Sismani
- Stavros Malas
- Violetta Christophidou‑Anastasiadou
- George A. Tanteles
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Affiliations: Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus, Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus, Department of Ophthalmology, Nicosia General Hospital, 2029 Nicosia, Cyprus, Department of Developmental and Functional Genetics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus
Published online on: June 5, 2018 https://doi.org/10.3892/mmr.2018.9126
Pages: 1623-1627
Copyright: © Syrimis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the clinical and mutational spectrum of aniridia in a cohort of 17 affected individuals from six families from Cyprus. Each proband was initially evaluated for copy number variants at the PAX6 locus and subsequently underwent PAX6 mutation screening. Sequence analysis of FOXC1 and PITX2 was performed in patients who did not carry a PAX6 mutation. The most common clinical features in the group of aniridia patients associated with aniridia were nystagmus, cataracts and glaucoma. PAX6 pathogenic mutations were identified in five out of six families (a diagnostic yield of 84%). Previously reported pathogenic mutations in PAX6 were identified in four families, which comprise p.R203*, p.R240* and p.R317*. In addition, a novel pathogenic variant (p.E220Gfs*23) was identified in a single family. No pathogenic mutations were detected in PAX6, FOXC1 or PITX2 in the only patient with a sporadic form of aniridia‑like phenotype, confirming the genetic heterogeneity associated with this disease. To the best of our knowledge this is the first report on the mutational spectrum of PAX6 in aniridia patients of Cypriot ancestry. Mutational screening of PAX6 serves a crucial role in distinguishing isolated from syndromic forms of aniridia, and it may therefore eliminate the need for renal ultrasound scan surveillance, delineate the phenotype and improve genetic counseling.

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