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Gillion et al. Rare Dis Orphan Drugs J 2023;2:11 Rare Disease and
DOI: 10.20517/rdodj.2022.23
Orphan Drugs Journal

Case Report Open Access

Biallelic cubilin pathogenic variants as a cause of «
benign » proteinuria: implications for clinical

management

1,3
1,2
Valentine Gillion , Karin Dahan , Nathalie Godefroid 2,4
1
Division of Nephrology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels B-1200, Belgium.
2
Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels B-1200, Belgium.
3
Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium.
4
Division of Pediatric Nephrology, Cliniques universitaires Saint-Luc, Brussels B-1200, Belgium.
Correspondence to: Dr Valentine Gillion, Division of Nephrology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10,
Brussels B-1200, Belgium. E-mail: valentine.gillion@uclouvain.be
How to cite this article: Gillion V, Dahan K, Godefroid N. Biallelic cubilin pathogenic variants as a cause of « benign » proteinuria:
implications for clinical management. Rare Dis Orphan Drugs J 2023;2:11. https://dx.doi.org/10.20517/rdodj.2022.23

Received: 15 Nov 2022 First Decision: 23 Feb 2023 Revised: 24 Apr 2023 Accepted: 8 May 2023 Published: 15 May 2023
Academic Editors: Daniel Scherman, Jacques S Beckmann Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
The recent description of a cohort with both adults and children harboring biallelic pathogenic variants of CUBN
changed the paradigm of the management of isolated proteinuria. Indeed, the detection of proteinuria in a patient,
regardless of age, often leads to an exhaustive check-up including kidney biopsy but also the prescription of renin-
angiotensin system (RAS) blockers to slow the progression of kidney disease. Patients with CUBN variants have
nondetrimental proteinuria and are non-responsive to RAS blockers. We herein describe 2 siblings treated for
isolated proteinuria for several years, eventually diagnosed with CUBN biallelic pathogenic variants (c.703 C > T
and c.10363-3A > G). We review the physio-pathological mechanisms of this newly discovered disease and
discuss implications for clinical management.

Keywords: Proteinuria, genetic kidney disease, cubilin, isolated albuminuria

INTRODUCTION
Discovering isolated proteinuria in a patient should lead to an appropriate work-up, including biological

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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