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

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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) identifier identifier identifier

  • 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
  • Marmara 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.