A role for OCRL in glomerular function and disease

Rebecca Preston, Richard W Naylor, Graham Stewart, Agnieszka Bierzynska, Moin A Saleem, Martin Lowe, Rachel Lennon

Research output: Contribution to journalArticle (Academic Journal)peer-review

8 Citations (Scopus)
115 Downloads (Pure)


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 languageEnglish
JournalPediatric Nephrology
Early online date6 Dec 2019
Publication statusE-pub ahead of print - 6 Dec 2019


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