April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract
Author Affiliations & Notes
  • B. Kloeckener-Gruissem
    Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
    Department of Biology, ETH, Zurich, Switzerland
  • J. Zuercher
    Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
  • J. Neidhardt
    Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
  • I. Magyar
    Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
  • A. T. Moore
    Moorefields Eye Hospital, London, United Kingdom
  • S. Bhattacharya
    Institute of Ophthalmology, University College London, London, United Kingdom
  • E. Heon
    The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • F. Munier
    Faculte de Biologie et Medecine,
    University of Lausanne, Lausanne, Switzerland
    Jules Gonin Eye Hospital, Lausanne, Switzerland
  • D. F. Schorderet
    Institute for Research in Ophthalmology,
    University of Lausanne, Lausanne, Switzerland
    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
  • W. Berger
    Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
  • Footnotes
    Commercial Relationships  B. Kloeckener-Gruissem, None; J. Zuercher, None; J. Neidhardt, None; I. Magyar, None; A.T. Moore, None; S. Bhattacharya, None; E. Heon, None; F. Munier, None; D.F. Schorderet, None; W. Berger, None.
  • Footnotes
    Support  SNSF#320030_127558 to FLM&DSF; NIHR and Special Trustees of Moorefields Eye Hospital London to SB and ATM
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4773. doi:
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      B. Kloeckener-Gruissem, J. Zuercher, J. Neidhardt, I. Magyar, A. T. Moore, S. Bhattacharya, E. Heon, F. Munier, D. F. Schorderet, W. Berger; Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4773.

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

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Abstract

Purpose: : Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients.

Methods: : Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR.

Results: : We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5’UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5’UTR region.

Conclusions: : Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

Keywords: cataract • gene/expression • genetics 
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