LRP4 mutations alter Wnt/beta-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; Jill Clayton-Smith; Raoul Hennekam; Peter Nürnberg; Joachim Herz; Samia A. Temtamy; Bernd Wollnik

doi:https://doi.org/10.1016/j.ajhg.2010.03.004

LRP4 mutations alter Wnt/beta-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 journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	696-706
Journal	American journal of human genetics
Volume	86
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2010.03.004
Publication status	Published - 2010

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https://doi.org/10.1016/j.ajhg.2010.03.004

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/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome. American journal of human genetics, 86(5), 696-706. https://doi.org/10.1016/j.ajhg.2010.03.004

@article{cb12d80de3ab4b158e71a17d488c8e89,

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

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",

author = "Yun Li and Barbara Pawlik and Nursel Elcioglu and Mona Aglan and H{\"u}lya Kayserili and G{\"o}khan Yigit and Ferda Percin and Frances Goodman and Gudrun N{\"u}rnberg and Asim Cenani and Jill Urquhart and Boi-Dinh Chung and Samira Ismail and Khalda Amr and Aslanger, {Ayca D.} and Christian Becker and Christian Netzer and Pete Scambler and Wafaa Eyaid and Hanan Hamamy and Jill Clayton-Smith and Raoul Hennekam and Peter N{\"u}rnberg and Joachim Herz and Temtamy, {Samia A.} and Bernd Wollnik",

year = "2010",

doi = "https://doi.org/10.1016/j.ajhg.2010.03.004",

language = "English",

volume = "86",

pages = "696--706",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

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, 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/beta-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

TY - JOUR

T1 - LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome

AU - Li, Yun

AU - Pawlik, Barbara

AU - Elcioglu, Nursel

AU - Aglan, Mona

AU - Kayserili, Hülya

AU - Yigit, Gökhan

AU - Percin, Ferda

AU - Goodman, Frances

AU - Nürnberg, Gudrun

AU - Cenani, Asim

AU - Urquhart, Jill

AU - Chung, Boi-Dinh

AU - Ismail, Samira

AU - Amr, Khalda

AU - Aslanger, Ayca D.

AU - Becker, Christian

AU - Netzer, Christian

AU - Scambler, Pete

AU - Eyaid, Wafaa

AU - Hamamy, Hanan

AU - Clayton-Smith, Jill

AU - Hennekam, Raoul

AU - Nürnberg, Peter

AU - Herz, Joachim

AU - Temtamy, Samia A.

AU - Wollnik, Bernd

PY - 2010

Y1 - 2010

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.ajhg.2010.03.004

DO - https://doi.org/10.1016/j.ajhg.2010.03.004

M3 - Article

C2 - 20381006

SN - 0002-9297

VL - 86

SP - 696

EP - 706

JO - American journal of human genetics

JF - American journal of human genetics

IS - 5

ER -