LRP4 Mutations Alter Wnt/β-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz Syndrome

Yun Li, 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 HamamyJill Clayton-Smith, Raoul Hennekam, Peter Nürnberg, Joachim Herz, Samia A. Temtamy, Bernd Wollnik

Research output: Contribution to journalArticle

100 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)696-706
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - May 14 2010


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Li, Y., Pawlik, B., Elcioglu, N., Aglan, M., Kayserili, H., Yigit, G., Percin, F., Goodman, F., Nürnberg, G., Cenani, A., Urquhart, J., Chung, B. D., Ismail, S., Amr, K., Aslanger, A. D., Becker, C., Netzer, C., Scambler, P., Eyaid, W., ... Wollnik, B. (2010). LRP4 Mutations Alter Wnt/β-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz Syndrome. American Journal of Human Genetics, 86(5), 696-706.