Severe Cenani–Lenz syndrome caused by loss of LRP4 function

Authors

  • Ariana Kariminejad,

    1. Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran
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  • Barbara Stollfuß,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
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  • Yun Li,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
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  • Nina Bögershausen,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
    3. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
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  • Karin Boss,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
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  • Raoul C.M. Hennekam,

    1. Department of Pediatrics and Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • Bernd Wollnik

    Corresponding author
    1. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
    2. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
    • Institute of Human Genetics, University of Cologne, Cologne, Germany
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  • The authors declare no conflict of interest.
  • Ariana Kariminejad and Barbara Stollfuß contributed equally to this work.

Correspondence to:

Prof. Bernd Wollnik, M.D., Institute of Human Genetics, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany.

E-mail: bwollnik@uni-koeln.de

Abstract

Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani–Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani–Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype–phenotype correlation. © 2013 Wiley Periodicals, Inc.

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