Functional analysis of BMP4 mutations identified in pediatric CAKUT patients

Mansoureh Tabatabaeifar, Karl Peter Schlingmann, Mieczyslaw Litwin, Sevinc Emre, Aysin Bakkaloglu, Otto Mehls, Corinne Antignac, Franz Schaefer, Stefanie Weber, A. Anarat, A. Bakkaloglu, F. Ozaltin, A. Peco-Antic, U. Querfeld, J. Gellermann, P. Sallay, D. Drozdz, K. E. Bonzel, A. M. Wingen, A. ZurowskaI. Balasz, F. Perfumo, A. Canepa, D. E. Müller-Wiefel, K. Zepf, G. Offner, B. Enke, O. Mehls, F. Schaefer, E. Wühl, C. Hadtstein, U. Berg, G. Celsi, S. Emre, A. Sirin, I. Bilge, S. Çaliskan, S. Mir, E. Serdaroglu, C. Greiner, H. Eichstädt, S. Wygoda, K. Hohbach-Hohenfellner, N. Jeck, G. Klaus, A. Appiani, G. Ardissino, S. Testa, G. Montini, C. Antignac, P. Niaudet, M. Charbit, J. Dusek, A. Caldas-Afonso, A. Teixeira, S. Picca, C. Matteucci, M. Wigger, M. Fischbach, J. Terzic, J. Fydryk, T. Urasinski, R. Coppo, L. Peruzzi, A. Jankauskiene, M. Litwin, M. Abuauba, R. Grenda, K. Arbeiter, T. J. Neuhaus

Research output: Contribution to journalArticle


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-BMP4mutation, which results in perinuclear endoplasmic reticulum (ER) accumulation and enhanced lysosomal degradation of Bmp4. This work further supports the role of mutations in BMP4for abnormalities of human kidney development.

Original languageEnglish
Pages (from-to)2361-2368
Number of pages8
JournalPediatric Nephrology
Issue number12
Publication statusPublished - 2009



  • Abnormal protein complex
  • Bone morphogenetic protein 4
  • Kidney development
  • Subcellular localization

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Tabatabaeifar, M., Schlingmann, K. P., Litwin, M., Emre, S., Bakkaloglu, A., Mehls, O., Antignac, C., Schaefer, F., Weber, S., Anarat, A., Bakkaloglu, A., Ozaltin, F., Peco-Antic, A., Querfeld, U., Gellermann, J., Sallay, P., Drozdz, D., Bonzel, K. E., Wingen, A. M., ... Neuhaus, T. J. (2009). Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatric Nephrology, 24(12), 2361-2368.