Pediatric Nephrology

, 24:2361

Functional analysis of BMP4 mutations identified in pediatric CAKUT patients


  • Mansoureh Tabatabaeifar
    • Pediatric NephrologyUniversity of Heidelberg Children’s Hospital
  • Karl-Peter Schlingmann
    • Pediatric NephrologyUniversity of Marburg Children’s Hospital
  • Mieczyslaw Litwin
    • Nephrology and Kidney Transplantation DepartmentChildren’s Memorial Health Hospital Warsaw
  • Sevinc Emre
    • Department of Pediatrics, Istanbul Medical FacultyUniversity of Istanbul
  • Aysin Bakkaloglu
    • Faculty of MedicineHacettepe University
  • Otto Mehls
    • Pediatric NephrologyUniversity of Heidelberg Children’s Hospital
  • Corinne Antignac
    • INSERM U574, Hôpital Necker-Enfants Malades
  • Franz Schaefer
    • Pediatric NephrologyUniversity of Heidelberg Children’s Hospital
    • Pediatric NephrologyUniversity of Heidelberg Children’s Hospital
    • University of Essen Children’s Hospital
  • ESCAPE Trial Group
Original Article

DOI: 10.1007/s00467-009-1287-6

Cite this article as:
Tabatabaeifar, M., Schlingmann, K., Litwin, M. et al. Pediatr Nephrol (2009) 24: 2361. doi:10.1007/s00467-009-1287-6


Human congenital anomalies of the kidney and urinary tract (CAKUT) represent the major causes of chronic renal failure (CRF) in children. This set of disorders comprises renal agenesis, hypoplasia, dysplastic or double kidneys, and/or malformations of the ureter. It has recently been shown that mutations in several genes, among them BMP4, are associated with hereditary renal developmental diseases. In BMP4, we formerly identified three missense mutations (S91C, T116S, N150K) in five pediatric CAKUT patients. These BMP4 mutations were subsequently studied in a cellular expression system, and here we present functional data demonstrating a lower level of messenger RNA (mRNA) abundance in Bmp4 mutants that indicates a possible negative feedback of the mutants on their own mRNA expression and/or stability. Furthermore, we describe the formation of alternative protein complexes induced by the S91C-BMP4 mutation, which results in perinuclear endoplasmic reticulum (ER) accumulation and enhanced lysosomal degradation of Bmp4. This work further supports the role of mutations in BMP4 for abnormalities of human kidney development.


Kidney developmentCAKUTBone morphogenetic protein 4Abnormal protein complexSubcellular localization

Copyright information

© IPNA 2009