Pediatric Nephrology

, 24:2361 | Cite as

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 WeberEmail author
  • ESCAPE Trial Group
Original Article


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 development CAKUT Bone morphogenetic protein 4 Abnormal protein complex Subcellular localization 



The authors acknowledge the Nikon Imaging Center at the University of Heidelberg. Financial support for this study was obtained from the Thyssen Foundation (AZ-, the Dietmar Hopp Foundation, and the European Commission (5th Framework Program, QLG1-CT-2002 00908).


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Copyright information

© IPNA 2009

Authors and Affiliations

  • Mansoureh Tabatabaeifar
    • 1
  • Karl-Peter Schlingmann
    • 2
  • Mieczyslaw Litwin
    • 3
  • Sevinc Emre
    • 4
  • Aysin Bakkaloglu
    • 5
  • Otto Mehls
    • 1
  • Corinne Antignac
    • 6
  • Franz Schaefer
    • 1
  • Stefanie Weber
    • 1
    • 7
    Email author
  • ESCAPE Trial Group
  1. 1.Pediatric NephrologyUniversity of Heidelberg Children’s HospitalHeidelbergGermany
  2. 2.Pediatric NephrologyUniversity of Marburg Children’s HospitalMarburgGermany
  3. 3.Nephrology and Kidney Transplantation DepartmentChildren’s Memorial Health Hospital WarsawWarsawPoland
  4. 4.Department of Pediatrics, Istanbul Medical FacultyUniversity of IstanbulIstanbulTurkey
  5. 5.Faculty of MedicineHacettepe UniversityAnkaraTurkey
  6. 6.INSERM U574, Hôpital Necker-Enfants MaladesParisFrance
  7. 7.University of Essen Children’s HospitalEssenGermany

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