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 (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)
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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 languageEnglish
    Pages (from-to)641-648
    Number of pages8
    JournalPediatric Nephrology
    Early online date6 Dec 2019
    DOIs
    Publication statusPublished - Apr 2020

    Keywords

    • FSGS
    • Glomerular disease
    • Lowe syndrome
    • OCRL
    • Podocyte
    • Proteinuria

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