188
Views
1
CrossRef citations to date
0
Altmetric
Mutation Report

Missense mutation in the PAX6 gene can cause a complex mild variable phenotype predominated by concomitant strabismus

ORCID Icon, , , , , , , , , & show all
Pages 88-96 | Received 22 Jun 2021, Accepted 25 Jul 2021, Published online: 03 Aug 2021

References

  • Parikh V, Shugart YY, Doheny KF, Zhang J, Li L, Williams J, Hayden D, Craig B, Capo H, Chamblee D, et al. A strabismus susceptibility locus on chromosome 7p. Proc Natl Acad Sci U S A. 2003;100(21):12283–88. doi:10.1073/pnas.2035118100.
  • Rice A, Nsengimana J, Simmons IG, Toomes C, Hoole J, Willoughby CE, Cassidy F, Williams GA, George ND, Sheridan E, et al. Replication of the recessive STBMS1 locus but with dominant inheritance. Invest Ophthalmol Vis Sci. 2009;50(7):3210–17. doi:10.1167/iovs.07-1631.
  • Shaaban S, MacKinnon S, Andrews C, Staffieri SE, Maconachie GDE, Chan W-M, Whitman MC, Morton SU, Yazar S, MacGregor S, et al. Genome-wide association study identifies a susceptibility locus for comitant esotropia and suggests a parent-of-origin effect. Invest Ophthalmol Vis Sci. 2018;59(10):4054–64. doi:10.1167/iovs.18-24082.
  • Plotnikov D, Shah RL, Rodrigues JN, Cumberland PM, Rahi JS, Hysi PG, Atan D, Williams C, Guggenheim JA, Eye UKB, et al. A commonly occurring genetic variant within the NPLOC4-TSPAN10-PDE6G gene cluster is associated with the risk of strabismus. Hum Genet. 2019;138:723–37.
  • Cotter SA, Varma R, Tarczy-Hornoch K, McKean-Cowdin R, Lin J, Wen G, Wei J, Borchert M, Azen SP, Torres M, et al. Risk factors associated with childhood strabismus: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies. Ophthalmology. 2011;118:2251–61.
  • Pathai S, Cumberland PM, Rahi JS. Prevalence of and early-life influences on childhood strabismus: findings from the Millennium Cohort Study. Arch Pediatr Adolesc Med. 2010;164(3):250–57. doi:10.1001/archpediatrics.2009.297
  • Yang M, Chen J, Shen T, Kang Y, Deng D, Lin X, Wu H, Chen Q, Ye X, Li J, et al. Clinical characteristics and surgical outcomes in patients with intermittent exotropia: a large sample study in south China. Medicine (Baltimore). 2016;95(5):e2590. doi:10.1097/MD.0000000000002590.
  • Tang SM, Chan RYT, Bin Lin S, Rong SS, Lau HHW, Lau WWY, Yip WWK, Chen LJ, Ko STC, Yam JCS, et al. Refractive errors and concomitant strabismus: a systematic review and meta-analysis. Sci Rep. 2016;6(1):35177. doi:10.1038/srep35177.
  • Sun T, Wang Z, Shen T, Yan J, Xie C, Li X. Characterization of intelligence in children with exotropia. Int J Environ Res Public Health. 2019;16(17):3008. doi:10.3390/ijerph16173008.
  • Ton CCT, 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. doi:10.1016/0092-8674(91)90284-6.
  • Hanson IM, Seawright A, Hardman K, Hodgson S, Zaletayev D, Fekete G, Heyningen VV. PAX6 mutations in aniridia. Hum Mol Genet. 1993;2(7):915–20. doi:10.1093/hmg/2.7.915.
  • Lima Cunha D, Arno G, Corton M, Moosajee M. 2019. The spectrum of PAX6 mutations and genotype-phenotype correlations in the eye. Genes (Basel). 10(12):1050. doi:10.3390/genes10121050.
  • Lim HT, Seo E-J, Kim G-H, Ahn H, Lee H-J, Shin KH, Lee J-K, Yoo H-W. Comparison between aniridia with and without PAX6 mutations: clinical and molecular analysis in 14 Korean patients with aniridia. Ophthalmology. 2012;119(6):1258–64. doi:10.1016/j.ophtha.2011.12.010.
  • Goolam S, Carstens N, Ross M, Bentley D, Lopes M, Peden J, Kingsbury Z, Tsogka E, Barlow R, Carmichael TR, et al. Familial congenital cataract, coloboma, and nystagmus phenotype with variable expression caused by mutation in PAX6 in a South African family. Mol Vis. 2018;24:407–13.
  • Tzoulaki I, White IM, Hanson IM. PAX6 mutations: genotype-phenotype correlations. BMC Genet. 2005;6(1):27. doi:10.1186/1471-2156-6-27
  • Lim HT, Kim DH, Kim H. PAX6 aniridia syndrome: clinics, genetics, and therapeutics. Curr Opin Ophthalmol. 2017;28(5):436–47. doi:10.1097/ICU.0000000000000405
  • Gronskov K, Rosenberg T, Sand A, Brondum-Nielsen K. Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. Eur J Hum Genet. 1999;7(3):274–86. doi:10.1038/sj.ejhg.5200308
  • Hingorani M, Williamson KA, Moore AT, Van Heyningen V. Detailed ophthalmologic evaluation of 43 Individuals with PAX6 mutations. Invest Ophthalmol Vis Sci. 2009;50(6):2581–90. doi:10.1167/iovs.08-2827
  • Hingorani M, Hanson I, Van Heyningen V. Aniridia. Eur J Hum Genet. 2012;20:1011–17. doi:10.1038/ejhg.2012.100.
  • 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;36:175–79.
  • Yahalom C, Blumenfeld A, Hendler K, Wussuki-Lior O, Macarov M, Shohat M, Khateb S. Mild aniridia phenotype: an under-recognized diagnosis of a severe inherited ocular disease. Graefes Arch Clin Exp Ophthalmol. 2018;256(11):2157–64. doi:10.1007/s00417-018-4119-1.
  • Hanson I, Churchill A, Love J, Axton R, Moore T, Clarke M, Meire F, van Heyningen V. Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations. Hum Mol Genet. 1999;8(2):165–72. doi:10.1093/hmg/8.2.165.
  • Chauhan BK, Medsinge A, Baumgartner MP, Scanga HL, Kamakari S, Gajdosova E, Camacho CJ, Nischal KK. Case series: pyramidal cataracts, intact irides and nystagmus from three novel PAX6 mutations. Am J Ophthalmol Case Rep. 2018;10:172–79.
  • Thomas S, Thomas MG, Andrews C, Chan WM, Proudlock FA, McLean RJ, Pradeep A, Engle EC, Gottlob I. Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation. Eur J Hum Genet. 2014;22:344–49.
  • Brown A, McKie M, Van Heyningen V, Prosser J. The Human PAX6 Mutation Database. Nucleic Acids Res. 1998;26:259–64. doi:10.1093/nar/26.1.259.
  • Azuma N, Hotta Y, Tanaka H, Yamada M. Missense mutations in the PAX6 gene in aniridia. Invest Ophthalmol Vis Sci. 1998;39:2524–28.
  • Gregory-Evans K, Cheong-Leen R, George SM, Xie J, Moosajee M, Colapinto P, Gregory-Evans CY. Non-invasive anterior segment and posterior segment optical coherence tomography and phenotypic characterization of aniridia. Can J Ophthalmol. 2011;46(4):337–44. doi:10.1016/j.jcjo.2011.06.011.
  • Xiao Y, Liu X, Yang C, Liu L, Guo X, Wang Q, Gong B. A novel PAX6 heterozygous mutation found in a Chinese family with congenital aniridia. Genet Test Mol Biomarkers. 2019;23(7):495–500. doi:10.1089/gtmb.2018.0334.
  • 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. doi:10.1038/eye.2016.326.
  • Wang GM, Prasov L, Al-Hasani H, Marrs CER, Tolia S, Wiinikka-Buesser L, Richards JE, Bohnsack BL. Phenotypic variation in a four-generation family with aniridia carrying a novel PAX6 mutation. J Ophthalmol. 2018;2018:5978293.
  • Jin C, et al. A recurrent PAX6 mutation is associated with aniridia and congenital progressive cataract in a Chinese family. Mol Vis. 2012;18:465–70.
  • Qiu -J-J, Zhang Q, Geng Z-X, Liu M, Zhong Z-L, Chen -J-J, Liu F. Identification of a novel PAX6 mutation in a Chinese family with aniridia. BMC Ophthalmol. 2019;19(1):10. doi:10.1186/s12886-018-1009-6.
  • Wolf MTF, Lorenz B, Winterpacht A, Drechsler M, Schumacher V, Royer-Pokora B, Blankenagel A, Zabel B, Wildhardt G. Ten novel mutations found in Aniridia. Hum Mutat. 1998;12(5):304–13. doi:10.1002/(SICI)1098-1004(1998)12:5<304::AID-HUMU3>3.0.CO;2-D.
  • Kruger JM, Mansouri B, Cestari DM. An update on the genetics of comitant strabismus. Semin Ophthalmol. 2013;28(5–6):438–41. doi:10.3109/08820538.2013.825298
  • Maconachie GD, Gottlob I, McLean RJ. Risk factors and genetics in common comitant strabismus: a systematic review of the literature. JAMA Ophthalmol. 2013;131:1179–86. doi:10.1001/jamaophthalmol.2013.4001.
  • Abouzeid H, Youssef MA, ElShakankiri N, Hauser P, Munier FL, Schorderet DF. PAX6 aniridia and interhemispheric brain anomalies. Mol Vis. 2009;15:2074–83.
  • Sisodiya SM, Free SL, Williamson KA, Mitchell TN, Willis C, Stevens JM, Kendall BE, Shorvon SD, Hanson IM, Moore AT, et al. PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet. 2001;28:214–16.
  • Mitchell TN, Free SL, Williamson KA, Stevens JM, Churchill AJ, Hanson IM, Shorvon SD, Moore AT, Van Heyningen V, Sisodiya SM, et al. Polymicrogyria and absence of pineal gland due to PAX6 mutation. Ann Neurol. 2003;53:658–63.
  • Bamiou D-E, Free SL, Sisodiya SM, Chong WK, Musiek F, Williamson KA, Van Heyningen V, Moore AT, Gadian D, Luxon LM, et al. Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations. Arch Pediatr Adolesc Med. 2007;161(5):463–69. doi:10.1001/archpedi.161.5.463.
  • Tang SM, Ma L, Lu SY, Wang YM, Kam KW, Tam POS, Young AL, Pang CP, Yam JCS, Chen LJ, et al. Association of the PAX6 gene with extreme myopia rather than lower grade myopias. Br J Ophthalmol. 2018;102(4):570–74. doi:10.1136/bjophthalmol-2017-311327.
  • Hood MP, Kerr NC, Smaoui N, Iannaccone A. Abnormal cone ERGs in a family with congenital nystagmus and photophobia harboring a p.X423Lfs mutation in the PAX6 gene. Doc Ophthalmol. 2015;130:157–64. doi:10.1007/s10633-014-9477-3.
  • Tremblay F, Gupta SK, De Becker I, Guernsey DL, Neumann PE. Effects of PAX6 mutations on retinal function: an electroretinographic study. Am J Ophthalmol. 1998;126:211–18. doi:10.1016/s0002-9394(98)00190-1.
  • Hittner HM, Riccardi VM, Ferrell RE, Borda RR, Justice J Jr. Variable expressivity in autosomal dominant aniridia by clinical, electrophysiologic, and angiographic criteria. Am J Ophthalmol. 1980;89:531–39. doi:10.1016/0002-9394(80)90062-8.
  • Wu L, Ma Q, Chen Y, Wu DZ, Luo T. Abnormalities of ERG in congenital aniridia. Yan Ke Xue Bao. 1991;7(151–152):119.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.