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BMC Ophthalmology

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Open Access 01-12-2019 | Cataract | Research article

Identification of a novel PAX6 mutation in a Chinese family with aniridia

Authors: Jing-Jing Qiu, Qian Zhang, Zi-xin Geng, Min Liu, Zi-lin Zhong, Jian-jun Chen, Fei Liu

Published in: BMC Ophthalmology | Issue 1/2019

Abstract

Background

This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese family with autosomal dominant aniridia.

Methods

The recruited family members underwent comprehensive routine and ophthalmic examinations, and Sanger sequencing was performed to screen the mutation in PAX6.

Results

A novel heterozygous PAX6 deletion c.435_445delTAGCGAAAAGC (p.Ser146ThrfsX9) in exon 7 was identified in all affected individuals, but this was absent in any of the unaffected family members and in the 200 unrelated controls.

Conclusion

A novel deletion in the PAX6 gene was identified in a Chinese family associated with aniridia, which expands the spectrum of the PAX6 mutation and its associated phenotype.

Neuhaus C, Betz C, Bergmann C, Bolz HJ. Genetics of congenital aniridia. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2014;111(12):1157–63. https://doi.org/10.1007/s00347-014-3059-3 German. PMID: 25475187.CrossRef

Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L. Aniridia. A review. Surv Ophthalmol. 1984;28(6):621–42 PMID: 6330922.CrossRef

Hu DN. Prevalence and mode of inheritance of major genetic eye diseases in China. J Med Genet. 1987;24(10):584–8 PMID: 3500313.CrossRef

Jordan T, Hanson I, Zaletayev D, Hodgson S, Prosser J, Seawright A, Hastie N, van Heyningen V. The human PAX6 gene is mutated in two patients with aniridia. Nat Genet. 1992;1(5):328–32. https://doi.org/10.1038/ng0892-328 PMID: 1302030.CrossRefPubMed

Brauner SC, Walton DS, Chen TC. Aniridia. Int Ophthalmol Clin. 2008;48(2):79–85. https://doi.org/10.1097/IIO.0b013e318169314b PMID: 18427263.CrossRefPubMed

Yahalom C, Sharon D, Dalia E, Simhon SB, Shemesh E, Blumenfeld A. Combined occurrence of autosomal dominant Aniridia and autosomal recessive albinism in several members of a family. Ophthalmic Genet. 2015;36(2):175–9. https://doi.org/10.3109/13816810.2015.1005318 PMID: 25687215.CrossRefPubMed

Ton CC, Hirvonen H, Miwa H, Weil MM, Monaghan P, Jordan T, van Heyningen V, Hastie ND, Meijers-Heijboer H, Drechsler M, et al. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell. 1991;67(6):1059–74 PMID: 1684738.CrossRef

Gronskov K, Olsen JH, Sand A, Pedersen W, Carlsen N, Bak Jylling AM, Lyngbye T, Brondum-Nielsen K, 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. 2001;109(1):11–8 PMID: 11479730.CrossRef

Robinson DO, Howarth RJ, Williamson KA, van Heyningen V, Beal SJ, 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. 2008;146A(5):558–69. https://doi.org/10.1002/ajmg.a.32209 PMID: 18241071.CrossRefPubMed

10.

Brown A, McKie M, van Heyningen V, Prosser J. The human PAX6 mutation database. Nucleic Acids Res. 1998;26(1):259–64 9399848.CrossRef

11.

Fantes J, Redeker B, Breen M, Boyle S, Brown J, Fletcher J, Jones S, Bickmore W, Fukushima Y, Mannens M, et al. Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Hum Mol Genet. 1995;4(3):415–22 PMID: 7795596.CrossRef

12.

Chien YH, Huang HP, Hwu WL, Chien YH, Chang TC, Lee NC. Eye anomalies and neurological manifestations in patients with PAX6 mutations. Mol Vis. 2009;15:2139–45 19898691.PubMedPubMedCentral

13.

Kokotas H, Petersen MB. Clinical and molecular aspects of aniridia. Clin Genet. 2010;77(5):409–20. https://doi.org/10.1111/j.1399-0004.2010.01372.x Epub 2010 Jan 6. Review. PMID: 20132240.CrossRefPubMed

14.

Mishra R, Gorlov IP, Chao LY, Singh S, Saunders GF. PAX6, paired domain influences sequence recognition by the homeodomain. J Biol Chem. 2002;277(51):49488–94 PMID: 12388550.CrossRef

15.

Li H, Leung CK, Wong L, Cheung CY, Pang CP, Weinreb RN, Lam DS. Comparative study of central corneal thickness measurement with slit-lamp optical coherence tomography and visante optical coherence tomography. Ophthalmology. 2008;115(5):796–801 e792 PMID: 17916376.CrossRef

16.

Ivanov I, Shuper A, Shohat M, Snir M, Weitz R. Aniridia: recent achievements in paediatric practice. Eur J Pediatr. 1995;154(10):795–800 PMID: 8529675.CrossRef

17.

Singh S, Chao LY, Mishra R, Davies J, Saunders GF. Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Hum Mol Genet. 2001;10(9):911–8 PMID: 11309364.CrossRef

18.

Nelson SM, Park L, Stenkamp DL. Retinal homeobox 1 is required for retinal neurogenesis and photoreceptor differentiation in embryonic zebrafish. Dev Biol. 2009;328(1):24–39. https://doi.org/10.1016/j.ydbio.2008.12.040 PMID: 19210961.CrossRefPubMedPubMedCentral

19.

Fisher M, Nakajima K, Odeleye AO, Zimmerman KB, Fish MB, Yaoita Y, Chojnowski JL, Lauderdale JD, Netland PA, Robert M. Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients Takuya Nakayama. Dev Biol. 2015;408(2):328–44. https://doi.org/10.1016/j.ydbio.2015.02.012 Grainger Dev Biol. Author manuscript; available in PMC 2016 Dec 15.Published in final edited form as: Published online 2015 Feb 25. PMCID: PMC4549229.CrossRefPubMedPubMedCentral

20.

Bobilev AM, McDougal ME, Taylor WL, Geisert EE, Peter A, Netland JD. Assessment of PAX6 alleles in 66 families with aniridia. Clin Genet. 2016;89(6):669–77. https://doi.org/10.1111/cge.12708 Published online 2016 Jan 25. Lauderdale Clin Genet. Author manuscript; available in PMC 2017 Jun 1.Published in final edited form as: PMCID: PMC4873406.CrossRefPubMedPubMedCentral

21.

Souzeau E, Rudkin AK, Dubowsky A, Casson RJ, Muecke JS, Mancel E, Whiting M, Mills RAD, Burdon KP, Craig JE. PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia. Mol Vis. 2018;24:261–73 Published online 2018 Mar 28. PMCID: PMC5873721.PubMedPubMedCentral

22.

Zhang R, Linpeng S, Wei X, Li H, Huang Y, Guo J, Wu Q, Liang D, Wu L. Novel variants in PAX6 gene caused congenital aniridia in two Chinese families. Eye (Lond). 2017;31(6):956–61. https://doi.org/10.1038/eye.2016.326 Published online 2017 Feb 3 PMCID: PMC5518831.CrossRef

Title: Identification of a novel PAX6 mutation in a Chinese family with aniridia
Authors: Jing-Jing Qiu
Qian Zhang
Zi-xin Geng
Min Liu
Zi-lin Zhong
Jian-jun Chen
Fei Liu
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Cataract
Published in: BMC Ophthalmology / Issue 1/2019
Electronic ISSN: 1471-2415
DOI: https://doi.org/10.1186/s12886-018-1009-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Identification of a novel PAX6 mutation in a Chinese family with aniridia

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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