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.
Citation
Preston, R., Naylor, R.W., Stewart, G., Bierzynska, A., Saleem, M.A., Lowe, M., Lennon, R. (2019) A role for OCRL in glomerular function and disease. Pediatric nephrology (Berlin, Germany). 35(4):641-648.
Abstract
Background 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.
Methods 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.
Results 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.
Conclusion 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping