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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.
Original language | English |
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Journal | Pediatric Nephrology |
Early online date | 6 Dec 2019 |
DOIs | |
Publication status | E-pub ahead of print - 6 Dec 2019 |
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Dive into the research topics of 'A role for OCRL in glomerular function and disease'. Together they form a unique fingerprint.Projects
- 2 Finished
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Study of trans-national cohorts of nephrotic syndrome to alleviate disease burden
1/04/17 → 31/12/20
Project: Research