Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants
© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA..
BACKGROUND: Proteinuria is a well-known risk factor for progressive kidney impairment. Recently, C-terminal cubilin (CUBN) variants have been associated with isolated proteinuria without progression of kidney disease.
METHODS: Genetic testing of 347 families with proteinuria of suspected monogenic cause was performed by next-generation sequencing of a custom-designed kidney disease gene panel. Families with CUBN biallelic proteinuria-causing variants were studied at the clinical, genetic, laboratory and pathologic levels.
RESULTS: Twelve families (15 patients) bearing homozygous or compound heterozygous proteinuria-causing variants in the C-terminal CUBN gene were identified, representing 3.5% of the total cohort. We identified 14 different sequence variants, five of which were novel. The median age at diagnosis of proteinuria was 4 years (range 9 months to 44 years), and in most cases proteinuria was detected incidentally. Thirteen patients had moderate to severe proteinuria at diagnosis without nephrotic syndrome. These patients showed lack of response to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, normal kidney biopsy and preservation of normal kidney function over time. The two remaining patients presented a more severe phenotype, likely caused by associated comorbidities.
CONCLUSIONS: Identification of C-terminal pathogenic CUBN variants is diagnostic of an entity characterized by glomerular proteinuria, normal kidney histology and lack of response to ACEi/ARB treatment. This study adds evidence and increases awareness about albuminuria caused by C-terminal variants in the CUBN gene, which is a benign condition usually diagnosed in childhood with preserved renal function until adulthood.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
|---|---|
| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 37(2022), 10 vom: 22. Sept., Seite 1906-1915 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Domingo-Gallego, Andrea [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 23.09.2022 Date Revised 26.10.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/ndt/gfab285 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM331513455 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM331513455 | ||
| 003 | DE-627 | ||
| 005 | 20231225213632.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/ndt/gfab285 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1105.xml |
| 035 | |a (DE-627)NLM331513455 | ||
| 035 | |a (NLM)34610128 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Domingo-Gallego, Andrea |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.09.2022 | ||
| 500 | |a Date Revised 26.10.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a BACKGROUND: Proteinuria is a well-known risk factor for progressive kidney impairment. Recently, C-terminal cubilin (CUBN) variants have been associated with isolated proteinuria without progression of kidney disease | ||
| 520 | |a METHODS: Genetic testing of 347 families with proteinuria of suspected monogenic cause was performed by next-generation sequencing of a custom-designed kidney disease gene panel. Families with CUBN biallelic proteinuria-causing variants were studied at the clinical, genetic, laboratory and pathologic levels | ||
| 520 | |a RESULTS: Twelve families (15 patients) bearing homozygous or compound heterozygous proteinuria-causing variants in the C-terminal CUBN gene were identified, representing 3.5% of the total cohort. We identified 14 different sequence variants, five of which were novel. The median age at diagnosis of proteinuria was 4 years (range 9 months to 44 years), and in most cases proteinuria was detected incidentally. Thirteen patients had moderate to severe proteinuria at diagnosis without nephrotic syndrome. These patients showed lack of response to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, normal kidney biopsy and preservation of normal kidney function over time. The two remaining patients presented a more severe phenotype, likely caused by associated comorbidities | ||
| 520 | |a CONCLUSIONS: Identification of C-terminal pathogenic CUBN variants is diagnostic of an entity characterized by glomerular proteinuria, normal kidney histology and lack of response to ACEi/ARB treatment. This study adds evidence and increases awareness about albuminuria caused by C-terminal variants in the CUBN gene, which is a benign condition usually diagnosed in childhood with preserved renal function until adulthood | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cubilin | |
| 650 | 4 | |a genetic testing | |
| 650 | 4 | |a inherited kidney diseases | |
| 650 | 4 | |a proteinuria | |
| 650 | 7 | |a Angiotensin Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a intrinsic factor-cobalamin receptor |2 NLM | |
| 700 | 1 | |a Pybus, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Madariaga, Leire |e verfasserin |4 aut | |
| 700 | 1 | |a Piñero-Fernández, Juan Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a González-Pastor, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a López-González, Mercedes |e verfasserin |4 aut | |
| 700 | 1 | |a Simarro-Rueda, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Quintanilla-Mata, María Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Matoses-Ruipérez, María Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Ejarque-Vila, Laia |e verfasserin |4 aut | |
| 700 | 1 | |a Cornec-Le Gall, Emilie |e verfasserin |4 aut | |
| 700 | 1 | |a Guirado, Lluís |e verfasserin |4 aut | |
| 700 | 1 | |a Torra, Roser |e verfasserin |4 aut | |
| 700 | 1 | |a Ariceta, Gema |e verfasserin |4 aut | |
| 700 | 1 | |a Ars, Elisabet |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association |d 1990 |g 37(2022), 10 vom: 22. Sept., Seite 1906-1915 |w (DE-627)NLM012639206 |x 1460-2385 |7 nnns |
| 773 | 1 | 8 | |g volume:37 |g year:2022 |g number:10 |g day:22 |g month:09 |g pages:1906-1915 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/ndt/gfab285 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 37 |j 2022 |e 10 |b 22 |c 09 |h 1906-1915 | ||