Clinical Findings in Family with Aniridia due the PAX6 Mutation
Authors:
L. Godavová 1; M. Godava 2; J. Sabová 3; G. Kolářová 1; Š. Mohlerová 1
Authors place of work:
Ústav lékařské genetiky, FN Olomouc
přednostka
doc. MUDr. Ishraq Dhaifalah, Ph. D.
; Oční oddělení, Vojenská nemocnice
Olomouc
primářka MUDr. Šárka Mohlerová
1; Ústav lékařské genetiky a fetální
medicíny, LF UP Olomouc
2; Sekce lidské genetiky
a celogenomového sekvenování
Synlab Genetics, s. r. o., Praha
vedoucí garant
MUDr. Soňa Peková, Ph. D.
3
Published in the journal:
Čes. a slov. Oftal., 70, 2014, No. 4, p. 138-144
Category:
Původní práce
Summary
Background:
inborn isolated aniridia is rare bilateral impairment of several eye structures manifesting mainly by absence of iris, photophobia and decreased visual acuity. There are also others ocular symptoms associated with aniridia such as nystagmus, strabismus, eyelid ptosis, amblyopia, serious refractive errors, anisometropia, corneal changes, impairment of the lens, chamber angle dysgenesis, optic nerve and macular hypoplasia and congenital or secondary glaucoma. The most frequent aetiology of this eye dysgenesis is mutation in PAX6. Aim of this report is to describe ocular findings in the family with familial aniridia (MIM #106210), to debate their severity, prognosis and therapy options.
Material and methods:
assessment of previous medical history and actual ophthalmological findings in 4 persons of 3 generation family with aniridia. According to the compliance, the patients underwent these tests: assessment of the visual acuity, intraocular pressure, refraction test, slit-lamp examination and biomicroscopy, pachymetry test and OCT examination. The genetic counselling was performed with subsequent PAX6 mutation analysis.
Results:
all of the examined aniridia family members showed severe symptoms of the disease, the aniridia and photophobia were present. Positive age related correlation showed progressive visual acuity decrease to the practical blindness due to aniridia-associated keratopathy, secondary glaucoma and cataract. DNA analysis revealed presence of p.Gln180X PAX6 mutation in all of the affected persons. The mutation leads to shortened and therefore non-functional protein.
Conclusions:
PAX6 mutations leading to premature termination of protein translation are frequently associated with severe symptoms of aniridia and small intrafamilial variability of ocular impairment. This fact is also well demonstrated in members of family described by this report, the symptoms are severe and progressing with age. Therapy is difficult and often with partial success, such in case of secondary glaucoma in young girl from this family. Any eye surgery must be individually judged due to risk of several post-operative complications. And more, the poor vision in aniridia patients is progressively worsening in time to practical blindness.
Key words:
aniridia, PAX6, macular hypoplasia, glaucoma
Zdroje
1. Bamiou, D.E., Free, S.L., Sisodiya, S.M.: 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): 463–469.
2. Bhatia, S., Bengani, H., Fish, M. et al.: Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia. Am J Hum Genet, 93: 1126-1134, 2013.
3. Brandt, J.D., Casuso, L.A., Budenz, D.L.: Markedly increased central corneal thickeness: an uncrecognized finding in congenital aniridia. AM J. Ophthalmol, 2004; 137(2): 348–350.
4. Socialstyrelsen. Congenital aniridia. [online]. 2012-06-19 [citováno 2014-05-15]. Dostupné z: < http://www.socialstyrelsen.se/rarediseases/congenitalaniridia>.
5. Ellison-Wright, Z., Heyman, I., Frampton, I. et al.: Heterozygous PAX6 mutation, adult brain structure and fronto-striato-thalamic function in a human family. Eur J Neurosci, 2004; 19(6): 1505–1512.
6. Free, S.L., Mitchell, T.N., Williamson, K.A. et al.: Quantitative MR image analysis in subjects with defects in the PAX6 gene. Neuroimage, 2003; 20(5): 2281–2290.
7. Glaser, T., Jepeal, L., Edwards, J.G. et al.: PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat Genet, 1994; 7(4): 463–471.
8. Grant, W.M. and Walton, D.S.: Progressive changes in the angle in congenital aniridia, with development of glaucoma. Trans Am Ophthalmol Soc, 1974; 72: 207–228.
9. Gregory-Evans, C.Y., Wang, X., Wasan, K.M.: Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects. J Clin Invest, 2014; 124(1): 111–116.
10. Hewitt, A.W., Kearns, L.S., Jamieson, R.V. et al.: PAX6 mutations may be associated with high myopia. Ophthalmic Genet, 2007; 28(3): 179–182.
11. Hingorani, M., Hanson, I., van Heyningen V.: Aniridia. Eur J Hum Genet, 2012; 20(10): 1011–1017.
12. Hodgson, S.V, Saunders, K.E.: A probable case of the homozygous condition of the aniridia gene. J Med Genet, 1980; 17(6): 478–480.
13. Holmström, G., Eriksson, U., Hellgren, K.: Optical coherence tomography is helpful in the diagnosis od foveal hypoplasia. Acta Ophthalmol, 2010; 88(4): 439–442.
14. Jastaneiah, S., Al-Rajhi, A.A.: Association of aniridia and dry eyes. Ophthalmology, 2005; 112(9): 1535–1540.
15. Margo, C.E.: Congenital aniridia: a histopathologic study of the anterior segment in children. J Pediatr Ophthalmol Strabismus, 1983; 20(5): 192–198.
16. Martha, A., Strong, L.C., Ferrell, R.E. et al.: Three novel aniridia mutations in the human PAX6 gene. Hum Mutat, 1995; 6(1): 44–49.
17. McGuire, D., Weinreb, R., Goldbaum, M.: Foveal hypoplasia demonstrated in vivo with optical coherence tomography. Am J Ophthal, 2003; 135(1): 112–114.
18. Mitchell, T.N., Free, S.L., Williamson, K.A. et al.: Polymicrogyria and absence of pineal gland due to PAX6 mutation. Ann Neurol, 2003; 53: 658–663.
19. Nelson, L.B., Spaeth, G.L., Nowinski, T.S. et al.: Aniridia. A review. Surv Ophthalmol, 1984; 28(6): 621–642.
20. Nishina, S., Kohsaka, S., Yamaguchi, Y. et al.: PAX6 expression in the developing human eye. Br J Ophthalmol, 1999; 83(6): 723–727.
21. Rush, C.C.: Congenital Aniridia. Trans Am Ophthalmol Soc. 1926;24:332-341.
22. Seefelder, R.: Die aniridie als eine entwicklungshemmung der retina. Albrecht Von Graefes Arch Klin Exp Ophthalmol, 1909; 70(1): 65–87.
23. Shaw M.W., Falls H.F., Neel J.V.: Congenital Aniridia. Am J Hum Genet, 1960; 12(4): 389–415.
24. Sisodiya, S.M., Free, S.L., Williamson, K.A. et al.: PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet, 2001; 28(3): 214–216.
25. Traboulsi, E.I.: Genetic diseases of the eye. 2nd ed. (Oxford Monographs on Medical Genetics). China: Oxford University Press Inc., 2012. 923 s. ISBN 978-0195326147.
26. Tremblay, F., Gupta, S.K., De Becker, I. et al.: Effects of PAX6 mutations on retinal function: an electroretinographic study. Am J Ophthalmol, 1998; 126(2): 211–218.
27. Tseng, S.C., Prabhasawat, P., Barton, K. et al: Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol, 1998; 116(4): 431-441.
28. Tzoulaki, I., White, I.M., Hanson, I.M.: PAX6 mutations: genotype-phenotype correlations. BMC Genet, 2005; 6: 27.
29. Vacek, Z.: Embryologie.1. vyd. Praha: Grada Publishing, 2006. 256 s. ISBN 978-80-247-1267-3. Kapitola 8.8, Vývoj smyslových orgánů, s. 231–238.
30. Valenzuela, A., Cline, R.A.: Ocular and nonocular findings in patients with aniridia. Can J Ophthalmol, 2004; 39(6): 632–638.
31. Wu, L., Ma, Q., Chen, Y. et al.: Abnormalities of ERG in congenital aniridia. Yan Ke Xue Bao, 1991; 7(3): 151–152.
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OftalmológiaČlánok vyšiel v časopise
Česká a slovenská oftalmologie
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