Linda M. Reis and Rebecca C. Tyler contributed equally to this work.
FOXE3 plays a significant role in autosomal recessive microphthalmia†
Article first published online: 5 FEB 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 3, pages 582–590, March 2010
How to Cite
Reis, L. M., Tyler, R. C., Schneider, A., Bardakjian, T., Stoler, J. M., Melancon, S. B. and Semina, E. V. (2010), FOXE3 plays a significant role in autosomal recessive microphthalmia. Am. J. Med. Genet., 152A: 582–590. doi: 10.1002/ajmg.a.33257
How to cite this article: Reis LM, Tyler RC, Schneider A, Bardakjian T, Stoler JM, Melancon SB, Semina EV. 2010. FOXE3 plays a significant role in autosomal recessive microphthalmia. Am J Med Genet Part A 152A:582–590.
- Issue published online: 22 FEB 2010
- Article first published online: 5 FEB 2010
- Manuscript Accepted: 13 NOV 2009
- Manuscript Received: 9 SEP 2009
- National Eye Institute. Grant Numbers: EY013606, EY015518
- Children's Research Institute Foundation at Children's Hospital of Wisconsin
- National Center for Research Resources. Grant Number: M01-RR00058
- Mellon Mid-Atlantic Charitable Trusts Albert B. Millett Memorial Fund and Rae S. Uber Trust
- Gustavus and Louis Pfeiffer Research Foundation
FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop normally. In humans, autosomal dominant and recessive mutations in FOXE3 have been associated with variable phenotypes including anterior segment anomalies, cataract, and microphthalmia. We undertook sequencing of FOXE3 in 116 probands with a spectrum of ocular defects ranging from anterior segment dysgenesis and cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found in four of 26 probands affected with bilateral microphthalmia (15% of all bilateral microphthalmia and 100% of consanguineous families with this phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or corneal defects; no other associated systemic anomalies were observed in FOXE3-positive families. The previously reported c.720C > A (p.C240X) nonsense mutation was identified in two additional families in our sample and therefore appears to be recurrent, now reported in three independent microphthalmia families of varied ethnic backgrounds. Several missense variants were identified at varying frequencies in patient and control groups with some apparently being race-specific, which underscores the importance of utilizing race/ethnicity-matched control populations in evaluating the relevance of genetic screening results. In conclusion, FOXE3 mutations represent an important cause of nonsyndromic autosomal recessive bilateral microphthalmia. © 2010 Wiley-Liss, Inc.