April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
The Identification of Mutations in the OTX2 Gene in Anophthalmia/Microphthalmia Patients
Author Affiliations & Notes
  • K. F. Schilter
    Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, Wisconsin
  • T. M. Bardakjian
    Genetics Division, Albert Einstein Medical Center, Philadelphia, Pennsylvania
  • A. Schneider
    Genetics Division, Albert Einstein Medical Center, Philadelphia, Pennsylvania
  • R. C. Tyler
    Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, Wisconsin
  • L. M. Reis
    Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, Wisconsin
  • E. V. Semina
    Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, Wisconsin
  • Footnotes
    Commercial Relationships  K.F. Schilter, None; T.M. Bardakjian, None; A. Schneider, None; R.C. Tyler, None; L.M. Reis, None; E.V. Semina, None.
  • Footnotes
    Support  NIH Grant EY015518
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4098. doi:
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    • Get Citation

      K. F. Schilter, T. M. Bardakjian, A. Schneider, R. C. Tyler, L. M. Reis, E. V. Semina; The Identification of Mutations in the OTX2 Gene in Anophthalmia/Microphthalmia Patients. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4098.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Anophthalmia and microphthalmia (A/M) are rare (1-19 of 10,000) developmental disorders associated with the absence of an eye or the presence of a small eye. A number of genes have been shown to be involved in A/M, with SOX2 mutations being the most common, at a mutation rate of about 25%. OTX2 is a homeodomain transcription factor that is important in eye and brain development. Mutations in OTX2 have also been reported in patients with A/M but there is varying data as to the mutation frequency. We screened A/M patient samples for mutations in OTX2 to determine the mutation spectrum and frequency in our population.

Methods: : A total of 50 human DNA samples collected from A/M patients were used in this study. The three OTX2 coding exons were amplified by PCR and used for direct sequencing.

Results: : We identified heterozygous mutations in four patients with A/M. Patients 1 and 2 have bilateral microphthalmia and were found to have, respectively, a 1-nt insertion within exon 4 and a C to T transition in exon 5; both mutations predicted to result in a premature termination of the protein. Patient 3 has anophthalmia in one eye and severe microphthalmia in the other eye and was found to carry G to A transition in exon 5 resulting in a premature stop codon and an A to T transversion resulting in an amino acid change immediately downstream of the stop codon mutation. Patient 4 displays bilateral microphthalmia and was identified to have a 4-nt insertion in exon 5 resulting in a frame shift and premature stop codon.

Conclusions: : Our screen identified mutations in 8% of the patients affected with A/M in our sample, which is higher than previously reported. All mutations identified in our study are predicted to result in a premature termination of the protein which is consistent with previous reports. Interestingly, in our study there appears to be a positive correlation between the more C-terminal position of mutation and the severity of the phenotype.

Keywords: gene screening • mutations • infant vision 
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