Pediatric Nephrology

, Volume 16, Issue 12, pp 1022–1029

Podocyte proteins in Galloway-Mowat syndrome

  • T. Srivastava
  • J. M. Whiting
  • R. E. Garola
  • M. J. Dasouki
  • V. Ruotsalainen
  • K. Tryggvason
  • R. Hamed
  • U. S. Alon
Genetic Renal Disease / Original Article

DOI: 10.1007/s004670100018

Cite this article as:
Srivastava, T., Whiting, J., Garola, R. et al. Pediatr Nephrol (2001) 16: 1022. doi:10.1007/s004670100018

Abstract.

Galloway-Mowat syndrome is an autosomal recessive disorder characterized by early onset nephrotic syndrome and central nervous system anomalies. Mutations in podocyte proteins, such as nephrin, α-actinin 4, and podocin, are associated with proteinuria and nephrotic syndrome. The genetic defect in Galloway-Mowat syndrome is as yet unknown. We postulated that in Galloway-Mowat syndrome the mutation would be in a protein that is expressed both in podocytes and neurons, such as synaptopodin, GLEPP1, or nephrin. We therefore analyzed kidney tissue from normal children (n=3), children with congenital nephrotic syndrome of the Finnish type (CNF, n=3), minimal change disease (MCD, n=3), focal segmental glomerulosclerosis (FSGS, n=3), and Galloway-Mowat syndrome (n=4) by immunohistochemistry for expression of synaptopodin, GLEPP1, intracellular domain of nephrin (nephrin-I), and extracellular domain of nephrin (nephrin-E). Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue. Nephrin was absent, and synaptopodin and GLEPP1 expression were decreased in CNF. The expression of all three proteins was reduced in MCD and FSGS; the decrease in expression being more marked in FSGS. Synaptopodin, GLEPP1, and nephrin expression was present, although reduced in Galloway-Mowat syndrome. We conclude that the reduced expression of synaptopodin, GLEPP1, and nephrin in Galloway- Mowat syndrome is a secondary phenomenon related to the proteinuria, and hence synaptopodin, GLEPP1, and nephrin are probably not the proteins mutated in Galloway-Mowat syndrome.

Keywords Galloway-Mowat syndromeSynaptopodinGLEPP1NephrinImmunohistochemistry

Copyright information

© IPNA - International Pediatric Nephrology Association New York, USA 2001

Authors and Affiliations

  • T. Srivastava
    • 1
  • J. M. Whiting
    • 2
  • R. E. Garola
    • 2
  • M. J. Dasouki
    • 3
  • V. Ruotsalainen
    • 4
  • K. Tryggvason
    • 5
  • R. Hamed
    • 6
  • U. S. Alon
    • 1
  1. 1.Section of Nephrology, The Children’s Mercy Hospital, University of Missouri at Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA. Ualon@cmh.eduUS
  2. 2.Department of Pathology, The Children’s Mercy Hospital, University of Missouri at Kansas City, USAUS
  3. 3.Section of Medical Genetics and Molecular Medicine, The Children’s Mercy Hospital, University of Missouri at Kansas City, USAUS
  4. 4.Department of Biochemistry, University of Oulu, FinlandFI
  5. 5.Division of Matrix Biology and Medical Biochemistry and Biophysics, Karolinska Institutet, SwedenSE
  6. 6.Department of Pediatrics, University of Jordan, Amman, JordanJO