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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
  • View Affiliations / Copyright

    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
    Copyright: © Syrimis et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1623-1627
    |
    Published online on: June 5, 2018
       https://doi.org/10.3892/mmr.2018.9126
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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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1 

Nelson LB, Spaeth GL, Nowinski TS, Margo CE and Jackson L: Aniridia. A review. Surv Ophthalmol. 28:621–642. 1984. View Article : Google Scholar : PubMed/NCBI

2 

Hingorani M and Moore A: AniridiaGeneReviews® [Internet]. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH and Stephens K: University of Washington Seattle; WA: 1993

3 

Grønskov K, Olsen JH, Sand A, Pedersen W, Carlsen N, Jylling Bak AM, Lyngbye T, Brøndum-Nielsen K and Rosenberg T: Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum Genet. 109:11–18. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Fischbach BV, Trout KL, Lewis J, Luis CA and Sika M: WAGR syndrome: A clinical review of 54 cases. Pediatrics. 116:984–988. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Valenzuela A and Cline RA: Ocular and nonocular findings in patients with aniridia. Can J Ophthalmol. 39:632–638. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Lee H, Khan R and O'Keefe M: Aniridia: Current pathology and management. Acta Ophthalmol. 86:708–715. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Hingorani M, Hanson I and van Heyningen V: Aniridia. Eur J Hum Genet. 20:1011–1017. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Sisodiya SM, Free SL, Williamson KA, Mitchell TN, Willis C, Stevens JM, Kendall BE, Shorvon SD, Hanson IM, Moore AT and van Heyningen V: PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet. 28:214–216. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Grant MK, Bobilev AM, Pierce JE, DeWitte J and Lauderdale JD: Structural brain abnormalities in 12 persons with aniridia. Version 2. F1000Res. 6:2552017. View Article : Google Scholar : PubMed/NCBI

10 

Jordan T, Hanson I, Zaletayev D, Hodgson S, Prosser J, Seawright A, Hastie N and van Heyningen V: The human PAX6 gene is mutated in two patients with aniridia. Nat Genet. 1:328–332. 1992. View Article : Google Scholar : PubMed/NCBI

11 

Robinson DO, Howarth RJ, Williamson KA, van Heyningen V, Beal SJ and Crolla JA: Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia. Am J Med Genet A. 146A:558–569. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Simpson TI and Price DJ: Pax6; a pleiotropic player in development. Bioessays. 24:1041–1051. 2002. View Article : Google Scholar : PubMed/NCBI

13 

van Heyningen V and Williamson KA: PAX6 in sensory development. Hum Mol Genet. 11:1161–1167. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Crolla JA and van Heyningen V: Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Am J Hum Genet. 71:1138–1149. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Perveen R, Lloyd IC, Clayton-Smith J, Churchill A, van Heyningen V, Hanson I, Taylor D, McKeown C, Super M, Kerr B, et al: Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations. Invest Ophthalmol Vis Sci. 41:2456–2460. 2000.PubMed/NCBI

16 

Khan AO, Aldahmesh MA and Al-Amri A: Heterozygous FOXC1 mutation (M161K) associated with congenital glaucoma and aniridia in an infant and a milder phenotype in her mother. Ophthalmic Genet. 29:67–71. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Ito YA, Footz TK, Berry FB, Mirzayans F, Yu M, Khan AO and Walter MA: Severe molecular defects of a novel FOXC1 W152G mutation result in aniridia. Invest Ophthalmol Vis Sci. 50:3573–3579. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Bobilev AM, McDougal ME, Taylor WL, Geisert EE, Netland PA and Lauderdale JD: Assessment of PAX6 alleles in 66 families with aniridia. Clin Genet. 89:669–677. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Primignani P, Allegrini D, Manfredini E, Romitti L, Mauri L, Patrosso MC, Veniani E, Franzoni A, Del Longo A, Gesu GP, et al: Screening of PAX6 gene in Italian congenital aniridia patients revealed four novel mutations. Ophthalmic Genet. 37:307–313. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Pérez-Solórzano S, Chacón-Camacho OF, Astiazarán MC, Ledesma-Gil G and Zenteno JC: PAX6 allelic heterogeneity in Mexican congenital aniridia patients: Expanding the mutational spectrum with seven novel pathogenic variants. Clin Exp Ophthalmol. 45:875–883. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Vasilyeva TA, Voskresenskaya AA, Käsmann-Kellner B, Khlebnikova OV, Pozdeyeva NA, Bayazutdinova GM, Kutsev SI, Ginter EK, Semina EV, Marakhonov AV and Zinchenko RA: Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations. Clin Genet. 92:639–644. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Vincent MC, Pujo AL, Olivier D and Calvas P: Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. Eur J Hum Genet. 11:163–169. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Bhuvanagiri M, Schlitter AM, Hentze MW and Kulozik AE: NMD: RNA biology meets human genetic medicine. Biochem J. 430:365–377. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Glaser T, Jepeal L, Edwards JG, Young SR, Favor J and Maas RL: PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat Genet. 7:463–471. 1994. View Article : Google Scholar : PubMed/NCBI

25 

Wilson DS, Guenther B, Desplan C and Kuriyan J: High resolution crystal structure of a paired (Pax) class cooperative homeodomain dimer on DNA. Cell. 82:709–719. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Xu HE, Rould MA, Xu W, Epstein JA, Maas RL and Pabo CO: Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev. 13:1263–1275. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Yokoi T, Nishina S, Fukami M, Ogata T, Hosono K, Hotta Y and Azuma N: Genotype-phenotype correlation of PAX6 gene mutations in aniridia. Hum Genome Var. 3:150522016. View Article : Google Scholar : PubMed/NCBI

28 

Reis LM, Tyler RC, Kloss Volkmann BA, Schilter KF, Levin AV, Lowry RB, Zwijnenburg PJ, Stroh E, Broeckel U, Murray JC and Semina EV: PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur J Hum Genet. 20:1224–1233. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Samant M, Chauhan BK, Lathrop KL and Nischal KK: Congenital aniridia: Etiology, manifestations and management. Exp Rev Ophthalmol. 11:135–144. 2016. View Article : Google Scholar

30 

Ansari M, Rainger J, Hanson IM, Williamson KA, Sharkey F, Harewood L, Sandilands A, Clayton-Smith J, Dollfus H, Bitoun P, et al: Genetic analysis of ‘PAX6-negative’ individuals with aniridia or gillespie syndrome. PLoS One. 11:e01537572016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Syrimis A, Nicolaou N, Alexandrou A, Papaevripidou I, Nicolaou M, Loukianou E, Sismani C, Malas S, Christophidou‑Anastasiadou V, Tanteles GA, Tanteles GA, et al: Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation. Mol Med Rep 18: 1623-1627, 2018.
APA
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E. ... Tanteles, G.A. (2018). Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation. Molecular Medicine Reports, 18, 1623-1627. https://doi.org/10.3892/mmr.2018.9126
MLA
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E., Sismani, C., Malas, S., Christophidou‑Anastasiadou, V., Tanteles, G. A."Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation". Molecular Medicine Reports 18.2 (2018): 1623-1627.
Chicago
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E., Sismani, C., Malas, S., Christophidou‑Anastasiadou, V., Tanteles, G. A."Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation". Molecular Medicine Reports 18, no. 2 (2018): 1623-1627. https://doi.org/10.3892/mmr.2018.9126
Copy and paste a formatted citation
x
Spandidos Publications style
Syrimis A, Nicolaou N, Alexandrou A, Papaevripidou I, Nicolaou M, Loukianou E, Sismani C, Malas S, Christophidou‑Anastasiadou V, Tanteles GA, Tanteles GA, et al: Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation. Mol Med Rep 18: 1623-1627, 2018.
APA
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E. ... Tanteles, G.A. (2018). Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation. Molecular Medicine Reports, 18, 1623-1627. https://doi.org/10.3892/mmr.2018.9126
MLA
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E., Sismani, C., Malas, S., Christophidou‑Anastasiadou, V., Tanteles, G. A."Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation". Molecular Medicine Reports 18.2 (2018): 1623-1627.
Chicago
Syrimis, A., Nicolaou, N., Alexandrou, A., Papaevripidou, I., Nicolaou, M., Loukianou, E., Sismani, C., Malas, S., Christophidou‑Anastasiadou, V., Tanteles, G. A."Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation". Molecular Medicine Reports 18, no. 2 (2018): 1623-1627. https://doi.org/10.3892/mmr.2018.9126
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