Skip to main content
Top
Published in: Pediatric Nephrology 6/2020

01-06-2020 | Anemia | Brief Report

Bi-allelic mutations in renin-angiotensin system genes, associated with renal tubular dysgenesis, can also present as a progressive chronic kidney disease

Authors: Marc Fila, Vincent Morinière, Philippe Eckart, Joelle Terzic, Marie-Claire Gubler, Corinne Antignac, Laurence Heidet

Published in: Pediatric Nephrology | Issue 6/2020

Login to get access

Abstract

Background

Bi-allelic loss of function variations in genes encoding proteins of the renin-angiotensin system (AGT, ACE, REN, AGTR1) are associated with autosomal recessive renal tubular dysgenesis, a severe disease characterized by the absence of differentiated proximal tubules leading to fetal anuria and neonatal end-stage renal disease.

Case-Diagnosis/Treatment

We identified bi-allelic loss of function mutations in ACE, the gene encoding angiotensin-converting enzyme, in 3 unrelated cases displaying progressive chronic renal failure, whose DNAs had been sent for suspicion of juvenile hyperuricemic nephropathy, nephronophthisis, and cystic renal disease, respectively. In all cases, patients were affected with anemia whose severity was unexpected regarding the level of renal failure and with important polyuro-polydipsia.

Conclusions

Bi-allelic loss of function mutation of ACE can have atypical and sometimes late presentation with chronic renal failure, anemia (out of proportion with the level of renal failure), and polyuro-polydipsia. These data illustrate the usefulness of next generation sequencing and “agnostic” approaches to elucidate cases with chronic kidney disease of unknown etiology and to broaden the spectrum of phenotypes of monogenic renal diseases. It also raises the question of genetic modifiers involved in the variation of the phenotypes associated with these mutations.
Appendix
Available only for authorised users
Literature
1.
go back to reference Heidet L, Morinière V, Henry C, De Tomasi L, Reilly ML, Humbert C, Alibeu O, Fourrage C, Bole-Feysot C, Nitschké P, Tores F, Bras M, Jeanpierre M, Pietrement C, Gaillard D, Gonzales M, Novo R, Schaefer E, Roume J, Martinovic J, Malan V, Salomon R, Saunier S, Antignac C, Jeanpierre C (2017) Targeted exome sequencing identifies PBX1 as involved in monogenic congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol 28:2901–2914CrossRef Heidet L, Morinière V, Henry C, De Tomasi L, Reilly ML, Humbert C, Alibeu O, Fourrage C, Bole-Feysot C, Nitschké P, Tores F, Bras M, Jeanpierre M, Pietrement C, Gaillard D, Gonzales M, Novo R, Schaefer E, Roume J, Martinovic J, Malan V, Salomon R, Saunier S, Antignac C, Jeanpierre C (2017) Targeted exome sequencing identifies PBX1 as involved in monogenic congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol 28:2901–2914CrossRef
2.
go back to reference Gribouval O, Morinière V, Pawtowski A, Arrondel C, Sallinen SL, Saloranta C, Clericuzio C, Viot G, Tantau J, Blesson S, Cloarec S, Machet MC, Chitayat D, Thauvin C, Laurent N, Sampson JR, Bernstein JA, Clemenson A, Prieur F, Daniel L, Levy-Mozziconacci A, Lachlan K, Alessandri JL, Cartault F, Rivière JP, Picard N, Baumann C, Delezoide AL, Belar Ortega M, Chassaing N, Labrune P, Yu S, Firth H, Wellesley D, Bitzan M, Alfares A, Braverman N, Krogh L, Tolmie J, Gaspar H, Doray B, Majore S, Bonneau D, Triau S, Loirat C, David A, Bartholdi D, Peleg A, Brackman D, Stone R, DeBerardinis R, Corvol P, Michaud A, Antignac C, Gubler MC (2012) Spectrum of mutations in the renin-angiotensin system genes in autosomalrecessive renal tubular dysgenesis. Hum Mutat 33:316–326CrossRef Gribouval O, Morinière V, Pawtowski A, Arrondel C, Sallinen SL, Saloranta C, Clericuzio C, Viot G, Tantau J, Blesson S, Cloarec S, Machet MC, Chitayat D, Thauvin C, Laurent N, Sampson JR, Bernstein JA, Clemenson A, Prieur F, Daniel L, Levy-Mozziconacci A, Lachlan K, Alessandri JL, Cartault F, Rivière JP, Picard N, Baumann C, Delezoide AL, Belar Ortega M, Chassaing N, Labrune P, Yu S, Firth H, Wellesley D, Bitzan M, Alfares A, Braverman N, Krogh L, Tolmie J, Gaspar H, Doray B, Majore S, Bonneau D, Triau S, Loirat C, David A, Bartholdi D, Peleg A, Brackman D, Stone R, DeBerardinis R, Corvol P, Michaud A, Antignac C, Gubler MC (2012) Spectrum of mutations in the renin-angiotensin system genes in autosomalrecessive renal tubular dysgenesis. Hum Mutat 33:316–326CrossRef
3.
go back to reference Schreiber R, Gubler MC, Gribouval O, Shalev H, Landau D (2010) Inherited renal tubular dysgenesis may not be universally fatal. Pediatr Nephrol 25:2531–2534CrossRef Schreiber R, Gubler MC, Gribouval O, Shalev H, Landau D (2010) Inherited renal tubular dysgenesis may not be universally fatal. Pediatr Nephrol 25:2531–2534CrossRef
4.
go back to reference Allanson JE, Pantzar JT, MacLeod PM (1983) Possible new autosomal recessive syndrome with unusual renal histopathological changes. Am J Med Genet 16:57–60CrossRef Allanson JE, Pantzar JT, MacLeod PM (1983) Possible new autosomal recessive syndrome with unusual renal histopathological changes. Am J Med Genet 16:57–60CrossRef
5.
go back to reference Lacoste M, Cai Y, Guicharnaud L, Mounier F, Dumez Y, Bouvier R, Dijoud F, Gonzales M, Chatten J, Delezoide AL, Daniel L, Joubert M, Laurent N, Aziza J, Sellami T, Amar HB, Jarnet C, Frances AM, Daïkha-Dahmane F, Coulomb A, Neuhaus TJ, Foliguet B, Chenal P, Marcorelles P, Gasc JM, Corvol P, Gubler MC (2006) Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: role of the renin-angiotensin system. J Am Soc Nephrol 17:2253–2263CrossRef Lacoste M, Cai Y, Guicharnaud L, Mounier F, Dumez Y, Bouvier R, Dijoud F, Gonzales M, Chatten J, Delezoide AL, Daniel L, Joubert M, Laurent N, Aziza J, Sellami T, Amar HB, Jarnet C, Frances AM, Daïkha-Dahmane F, Coulomb A, Neuhaus TJ, Foliguet B, Chenal P, Marcorelles P, Gasc JM, Corvol P, Gubler MC (2006) Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: role of the renin-angiotensin system. J Am Soc Nephrol 17:2253–2263CrossRef
6.
7.
go back to reference Uematsu M, Sakamoto O, Nishio T, Ohura T, Matsuda T, Inagaki T, Abe T, Okamura K, Kondo Y, Tsuchiya S (2006) A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations. Am J Med Genet A 140:2355–2360CrossRef Uematsu M, Sakamoto O, Nishio T, Ohura T, Matsuda T, Inagaki T, Abe T, Okamura K, Kondo Y, Tsuchiya S (2006) A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations. Am J Med Genet A 140:2355–2360CrossRef
8.
go back to reference Zingg-Schenk A, Bacchetta J, Corvol P, Michaud A, Stallmach T, Cochat P, Gribouval O, Gubler MC, Neuhaus TJ (2008) Inherited renal tubular dysgenesis: the first patients surviving the neonatal period. Eur J Pediatr 167:311–316CrossRef Zingg-Schenk A, Bacchetta J, Corvol P, Michaud A, Stallmach T, Cochat P, Gribouval O, Gubler MC, Neuhaus TJ (2008) Inherited renal tubular dysgenesis: the first patients surviving the neonatal period. Eur J Pediatr 167:311–316CrossRef
9.
go back to reference Uematsu M, Sakamoto O, Ohura T, Shimizu N, Satomura K, Tsuchiya S (2009) A further case of renal tubular dysgenesis surviving the neonatal period. Eur J Pediatr 168:207–209CrossRef Uematsu M, Sakamoto O, Ohura T, Shimizu N, Satomura K, Tsuchiya S (2009) A further case of renal tubular dysgenesis surviving the neonatal period. Eur J Pediatr 168:207–209CrossRef
10.
go back to reference Kim SY, Kang HG, Kim EK, Choi JH, Choi Y, Cheong HI (2012) Survival over 2 years of autosomal-recessive renal tubular dysgenesis. Clin Kidney J 5:56–58CrossRef Kim SY, Kang HG, Kim EK, Choi JH, Choi Y, Cheong HI (2012) Survival over 2 years of autosomal-recessive renal tubular dysgenesis. Clin Kidney J 5:56–58CrossRef
11.
go back to reference Cheungpasitporn W, Thongprayoon C, Chiasakul T, Korpaisarn S, Erickson SB (2015) Renin-angiotensin system inhibitors linked to anemia: a systematic review and meta-analysis. QJM 108:879–884CrossRef Cheungpasitporn W, Thongprayoon C, Chiasakul T, Korpaisarn S, Erickson SB (2015) Renin-angiotensin system inhibitors linked to anemia: a systematic review and meta-analysis. QJM 108:879–884CrossRef
12.
go back to reference Hubert C, Savary K, Gasc JM, Corvol P (2006) The hematopoietic system: a new niche for the renin-angiotensin system. Nat Clin Pract Cardiovasc Med 3:80–85CrossRef Hubert C, Savary K, Gasc JM, Corvol P (2006) The hematopoietic system: a new niche for the renin-angiotensin system. Nat Clin Pract Cardiovasc Med 3:80–85CrossRef
13.
go back to reference Donnelly S, Shah BR (1999) Erythropoietin deficiency in hyporeninemia. Am J Kidney Dis 33:947–953CrossRef Donnelly S, Shah BR (1999) Erythropoietin deficiency in hyporeninemia. Am J Kidney Dis 33:947–953CrossRef
14.
go back to reference Zivná M, Hůlková H, Matignon M, Hodanová K, Vylet'al P, Kalbácová M, Baresová V, Sikora J, Blazková H, Zivný J, Ivánek R, Stránecký V, Sovová J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gübler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S (2009) Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet 85:204–213CrossRef Zivná M, Hůlková H, Matignon M, Hodanová K, Vylet'al P, Kalbácová M, Baresová V, Sikora J, Blazková H, Zivný J, Ivánek R, Stránecký V, Sovová J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gübler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S (2009) Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet 85:204–213CrossRef
15.
go back to reference Uehara Y, Miura S, Yahiro E, Saku K (2013) Non-ACE pathway-induced angiotensin II production. Curr Pharm Des 19:3054–3059CrossRef Uehara Y, Miura S, Yahiro E, Saku K (2013) Non-ACE pathway-induced angiotensin II production. Curr Pharm Des 19:3054–3059CrossRef
16.
go back to reference Schütz S, Le Moullec JM, Corvol P, Gasc JM (1996) Early expression of all the components of the renin-angiotensin-system in human development. Am J Pathol 149:2067–2079PubMedPubMedCentral Schütz S, Le Moullec JM, Corvol P, Gasc JM (1996) Early expression of all the components of the renin-angiotensin-system in human development. Am J Pathol 149:2067–2079PubMedPubMedCentral
Metadata
Title
Bi-allelic mutations in renin-angiotensin system genes, associated with renal tubular dysgenesis, can also present as a progressive chronic kidney disease
Authors
Marc Fila
Vincent Morinière
Philippe Eckart
Joelle Terzic
Marie-Claire Gubler
Corinne Antignac
Laurence Heidet
Publication date
01-06-2020
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-020-04524-4

Other articles of this Issue 6/2020

Pediatric Nephrology 6/2020 Go to the issue