Loss of podocalyxin causes a novel syndromic type of congenital nephrotic syndrome

Exp Mol Med. 2017 Dec 15;49(12):e414. doi: 10.1038/emm.2017.227.


Many cellular structures directly imply specific biological functions. For example, normal slit diaphragm structures that extend from podocyte foot processes ensure the filtering function of renal glomeruli. These slits are covered by a number of surface proteins, such as nephrin, podocin, podocalyxin and CD2AP. Here we report a human patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL, which encodes podocalyxin, inherited from each parent. This set of symptoms strikingly mimics previously reported mouse Podxl-/- embryos, emphasizing the essential function of PODXL in mammalian kidney development and highlighting this patient as a human PODXL-null model. The results underscore the utility of current genomics approaches to provide insights into the genetic mechanisms of human disease traits through molecular diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Cytoskeletal Proteins / genetics
  • Disease Models, Animal
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney Glomerulus / metabolism
  • Membrane Proteins / genetics*
  • Mice
  • Mutation
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Sialoglycoproteins / genetics*


  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Sialoglycoproteins
  • nephrin
  • podocalyxin

Supplementary concepts

  • Nephrosis, congenital