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Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene

Authors

  • S. Moalem,

    1. Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children
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    • These authors contributed equally to this work.
  • P. Brouillard,

    1. Laboratory of Human Molecular Genetics
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    • These authors contributed equally to this work.
  • D. Kuypers,

    1. Department of Nephrology and Renal Transplantation, University Hospital Gasthuisberg, Leuven, Belgium
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  • E. Legius,

    1. Department of Human Genetics, KU Leuven, University Hospitals Leuven, Leuven, Belgium
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  • E. Harvey,

    1. Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, University of Toronto
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  • G. Taylor,

    1. Department of Pediatrics, Division of Pathology and laboratory Medicine, The Hospital for Sick Children
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  • M. Francois,

    1. The University of Queensland, St Lucia Campus, Brisbane, Australia
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  • M. Vikkula,

    1. Laboratory of Human Molecular Genetics
    2. Walloon Excellence in Life Sciences and Biotechnology (WELBIO), de Duve Institute Université catholique de Louvain, Brussels, Belgium
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    • These authors contributed equally to this work.
  • D. Chitayat

    Corresponding author
    1. Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children
    2. Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • Corresponding author: Dr D. Chitayat, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Ontario Hydro Generation Building, 700 University Avenue, 3rd floor, Rm. 3292, Toronto, Ontario, Canada.

      Tel.: +416 586 4523;

      fax: +416 586 4723;

      e-mail: dchitayat@mtsinai.on.ca

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    • These authors contributed equally to this work.

  • The authors declare that they have no conflict of interest.

Abstract

SOX18 mutations in humans are associated with both recessive and dominant hypotrichosis–lymphedema–telangiectasia syndrome (HLTS). We report two families with affected children carrying a SOX18 mutation: a living patient and his stillborn brother from Canada and a Belgian patient. The two living patients were diagnosed with HLTS and DNA analysis for the SOX18 gene showed that both had the identical heterozygous C > A transversion, resulting in a pre-mature truncation of the protein, lacking the transactivation domain. Both living patients developed renal failure with severe hypertension in childhood for which both underwent renal transplantation. To our best knowledge this is the first report of renal failure associated with heterozygous mutations in the SOX18 gene. We conclude that this specific mutation results in a new, autosomal dominant condition and propose the acronym HLT-renal defect syndrome for HLTRS.

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