2. Academic Validation
  3. LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome

LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome

  • Am J Hum Genet. 2010 May 14;86(5):696-706. doi: 10.1016/j.ajhg.2010.03.004.
Yun Li 1,  Barbara Pawlik,  Nursel Elcioglu,  Mona Aglan,  Hülya Kayserili,  Gökhan Yigit,  Ferda Percin,  Frances Goodman,  Gudrun Nürnberg,  Asim Cenani,  Jill Urquhart,  Boi-Dinh Chung,  Samira Ismail,  Khalda Amr,  Ayca D Aslanger,  Christian Becker,  Christian Netzer,  Pete Scambler,  Wafaa Eyaid,  Hanan Hamamy,  Jill Clayton-Smith,  Raoul Hennekam,  Peter Nürnberg,  Joachim Herz,  Samia A Temtamy,  Bernd Wollnik
Affiliations

Affiliation

  • 1 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
PMID: 20381006 DOI: 10.1016/j.ajhg.2010.03.004
Abstract

Cenani-Lenz syndrome (CLS) is an autosomal-recessive congenital disorder affecting distal limb development. It is characterized mainly by syndactyly and/or oligodactyly and is now shown to be commonly associated with kidney anomalies. We used a homozygosity-mapping approach to map the CLS1 locus to chromosome 11p11.2-q13.1. By sequencing candidate genes, we identified recessive LRP4 mutations in 12 families with CLS. LRP4 belongs to the low-density lipoprotein (LDL) receptor-related proteins (LRPs), which are essential for various developmental processes. LRP4 is known to antagonize LRP6-mediated activation of canonical Wnt signaling, a function that is lost by the identified mutations. Our findings increase the spectrum of congenital anomalies associated with abnormal lipoprotein receptor-dependent signaling.

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