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 Hamamy & 6 others Jill Clayton-Smith, Raoul Hennekam, Peter Nürnberg, Joachim Herz, Samia A. Temtamy, Bernd Wollnik

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)696-706
Number of pages11
JournalAmerican Journal of Human Genetics
Volume86
Issue number5
DOIs
StatePublished - May 14 2010

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Catenins
Extremities
LDL-Receptor Related Proteins
Lipoprotein Receptors
Syndactyly
Kidney
Recessive Genes
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Mutation
LDL Receptors
Chromosomes
Syndromic 1 Microphthalmia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

LRP4 Mutations Alter Wnt/β-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz Syndrome. / Li, Yun; Pawlik, Barbara; Elcioglu, Nursel; Aglan, Mona; Kayserili, Hülya; Yigit, Gökhan; Percin, Ferda; Goodman, Frances; Nürnberg, Gudrun; Cenani, Asim; Urquhart, Jill; Chung, Boi Dinh; Ismail, Samira; Amr, Khalda; Aslanger, Ayca D.; Becker, Christian; Netzer, Christian; Scambler, Pete; Eyaid, Wafaa; Hamamy, Hanan; Clayton-Smith, Jill; Hennekam, Raoul; Nürnberg, Peter; Herz, Joachim; Temtamy, Samia A.; Wollnik, Bernd.

In: American Journal of Human Genetics, Vol. 86, No. 5, 14.05.2010, p. 696-706.

Research output: Contribution to journalArticle

Li, Y, Pawlik, B, Elcioglu, N, Aglan, M, Kayserili, H, Yigit, G, Percin, F, Goodman, F, Nürnberg, G, Cenani, A, Urquhart, J, Chung, BD, Ismail, S, Amr, K, Aslanger, AD, Becker, C, Netzer, C, Scambler, P, Eyaid, W, Hamamy, H, Clayton-Smith, J, Hennekam, R, Nürnberg, P, Herz, J, Temtamy, SA & 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, vol. 86, no. 5, pp. 696-706. https://doi.org/10.1016/j.ajhg.2010.03.004
Li, Yun ; Pawlik, Barbara ; Elcioglu, Nursel ; Aglan, Mona ; Kayserili, Hülya ; Yigit, Gökhan ; Percin, Ferda ; Goodman, Frances ; Nürnberg, Gudrun ; Cenani, Asim ; Urquhart, Jill ; Chung, Boi Dinh ; Ismail, Samira ; Amr, Khalda ; Aslanger, Ayca D. ; Becker, Christian ; Netzer, Christian ; Scambler, Pete ; Eyaid, Wafaa ; Hamamy, Hanan ; Clayton-Smith, Jill ; Hennekam, Raoul ; Nürnberg, Peter ; Herz, Joachim ; Temtamy, Samia A. ; Wollnik, Bernd. / LRP4 Mutations Alter Wnt/β-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz Syndrome. In: American Journal of Human Genetics. 2010 ; Vol. 86, No. 5. pp. 696-706.
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AU - Clayton-Smith, Jill

AU - Hennekam, Raoul

AU - Nürnberg, Peter

AU - Herz, Joachim

AU - Temtamy, Samia A.

AU - Wollnik, Bernd

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