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

Li, Yun; Pawlik, Barbara; Elcioglu, Nursel; Aglan, Mona; Kayserili, Huelya; Yigit, Goekhan; PERÇİN, FERDA; Goodman, Frances; Nuernberg, Gudrun; Cenani, Asim; Urquhart, Jill; Chung, Boi-Dinh; Ismail, Samira; Amr, Khalda; Aslanger, Ayca; Becker, Christian; Netzer, Christian; Scambler, Pete; Eyaid, Wafaa; Hamamy, Hanan; Clayton-Smith, Jill; Hennekam, Raoul; Nuernberg, Peter; Herz, Joachim; Temtamy, Samia; Wollnik, Bernd

doi:10.1016/j.ajhg.2010.03.004

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

Li Y., Pawlik B., Elcioglu N., Aglan M., Kayserili H., Yigit G., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.86, sa.5, ss.696-706, 2010 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 86 Sayı: 5
Basım Tarihi: 2010
Doi Numarası: 10.1016/j.ajhg.2010.03.004
Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
Sayfa Sayıları: ss.696-706
Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
Gazi Üniversitesi Adresli: Evet

Özet

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.