FOXE3 plays a significant role in autosomal recessive microphthalmia

Authors

  • Linda M. Reis,

    1. Department of Pediatrics and Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226
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    • Linda M. Reis and Rebecca C. Tyler contributed equally to this work.

  • Rebecca C. Tyler,

    1. Department of Pediatrics and Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226
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    • Linda M. Reis and Rebecca C. Tyler contributed equally to this work.

  • Adele Schneider,

    1. Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, Pennsylvania
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  • Tanya Bardakjian,

    1. Division of Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, Pennsylvania
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  • Joan M. Stoler,

    1. Division of Genetics, Department of Medicine, Children's Hospital, Boston, Massachusetts
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  • Serge B. Melancon,

    1. Department of Medical Genetics, McGill University Health Centre, Montreal Children's Hospital, Montreal, Canada
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  • Elena V. Semina

    Corresponding author
    1. Department of Pediatrics and Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226
    2. Department of Cell Biology, Neurobiology and Anatomy at the Medical College of Wisconsin, Milwaukee, Wisconsin
    • C3520, Translational and Biomedical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509.
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  • 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.

Abstract

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.

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