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  • 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.

American journal of human genetics (2010-04-13)
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 Hamamy, Jill Clayton-Smith, Raoul Hennekam, Peter Nürnberg, Joachim Herz, Samia A Temtamy, Bernd Wollnik
PMID20381006
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.