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Open Access 01-04-2020 | Original Article

A role for OCRL in glomerular function and disease

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

Published in: Pediatric Nephrology | Issue 4/2020

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.

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Title: A role for OCRL in glomerular function and disease
Authors: Rebecca Preston
Richard W Naylor
Graham Stewart
Agnieszka Bierzynska
Moin A Saleem
Martin Lowe
Rachel Lennon
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 4/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-019-04317-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A role for OCRL in glomerular function and disease

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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