PUBLICATION

A role for OCRL in glomerular function and disease

Authors
Preston, R., Naylor, R.W., Stewart, G., Bierzynska, A., Saleem, M.A., Lowe, M., Lennon, R.
ID
ZDB-PUB-191212-1
Date
2019
Source
Pediatric nephrology (Berlin, Germany)   35(4): 641-648 (Journal)
Registered Authors
Lennon, Rachel, Lowe, Martin, Naylor, Richard
Keywords
FSGS, Glomerular disease, Lowe syndrome, OCRL, Podocyte, Proteinuria
MeSH Terms
  • Animals
  • Child
  • Chloride Channels
  • Exome Sequencing
  • Glomerulosclerosis, Focal Segmental/complications
  • Glomerulosclerosis, Focal Segmental/genetics*
  • Humans
  • Kidney Glomerulus/metabolism*
  • Male
  • Mutation
  • Oculocerebrorenal Syndrome/complications
  • Oculocerebrorenal Syndrome/genetics*
  • Phosphoric Monoester Hydrolases
  • Podocytes/metabolism
  • Proteinuria/etiology
  • Zebrafish
PubMed
31811534 Full text @ Pediatr. Nephrol.
Abstract
Lowe syndrome and Dent-2 disease are caused by mutations in the OCRL gene, which encodes for an inositol 5-phosphatase. The renal phenotype associated with OCRL mutations typically comprises a selective proximal tubulopathy, which can manifest as Fanconi syndrome in the most extreme cases.
Here, we report a 12-year-old male with nephrotic-range proteinuria and focal segmental glomerulosclerosis on renal biopsy. As a glomerular pathology was suspected, extensive investigation of tubular function was not performed.
Surprisingly, whole exome sequencing identified a genetic variant in OCRL (c1467-2A>G) that introduced a novel splice mutation leading to skipping of exon 15. In situ hybridisation of adult human kidney tissue and zebrafish larvae showed OCRL expression in the glomerulus, supporting a role for OCRL in glomerular function. In cultured podocytes, we found that OCRL associated with the linker protein IPIP27A and CD2AP, a protein that is important for maintenance of the podocyte slit diaphragm.
Taken together, this work suggests a previously under-appreciated role for OCRL in glomerular function and highlights the importance of investigating tubular function in patients with persistent proteinuria.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping