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Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis
Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis
Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme) and AGTR1 (angiotensin II receptor type 1). Here we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allows genetic counselling and early prenatal diagnosis.
1059-7794
316-326
Gribouval, Olivier
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Morinière, Vincent
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Gribouval, Olivier
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Pawtowski, Audrey
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Sampson, Julian R.
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Clemenson, Alix
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Lachlan, Katherine
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Alessandri, Jean Luc
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Cartault, François
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Rivière, Jean Pierre
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Picard, Nicole
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Baumann, Clarisse
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Loirat, Chantal
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Stone, Rosario
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DeBerardinis, Ralph
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Corvol, Pierre
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Michaud, Annie
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Gribouval, Olivier, Morinière, Vincent, Pawtowski, Audrey, Arrondel, Christelle, Sallinen, Satu-Leena, Saloranta, Carola, Clericuzio, Carol, Viot, Géraldine, Tantau, Julia, Blesson, Sophie, Cloarec, Sylvie, Machet, Marie Christine, Chitayat, David, Thauvin, Christelle, Laurent, Nicole, Sampson, Julian R., Bernstein, Jonathan A, Clemenson, Alix, Prieur, Fabienne, Daniel, Laurent, Levy-Mozziconacci, Annie, Lachlan, Katherine, Alessandri, Jean Luc, Cartault, François, Rivière, Jean Pierre, Picard, Nicole, Baumann, Clarisse, Delezoide, Anne Lise, Ortega, Maria Belar, Chassaing, Nicolas, Labrune, Philippe, Yu, Sui, Firth, Helen, Wellesley, Diana, Bitzan, Martin, Alfares, Ahmed, Braverman, Nancy, Krogh, Lotte, Tolmie, John, Gaspar, Harald, Doray, Bérénice, Majore, Silvia, Bonneau, Dominique, Triau, Stéphane, Loirat, Chantal, David, Albert, Bartholdi, Deborah, Peleg, Amir, Brackman, Damien, Stone, Rosario, DeBerardinis, Ralph, Corvol, Pierre, Michaud, Annie, Antignac, Corinne and Gubler, Marie Claire (2012) Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. Human Mutation, 33 (2), 316-326. (doi:10.1002/humu.21661). (PMID:22095942)

Record type: Article

Abstract

Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme) and AGTR1 (angiotensin II receptor type 1). Here we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allows genetic counselling and early prenatal diagnosis.

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More information

Accepted/In Press date: 17 November 2011
Published date: February 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 203955
URI: http://eprints.soton.ac.uk/id/eprint/203955
ISSN: 1059-7794
PURE UUID: 41f98e66-39f4-48c7-a291-4618a6156eaf

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Date deposited: 22 Nov 2011 11:37
Last modified: 14 Mar 2024 04:29

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Contributors

Author: Olivier Gribouval
Author: Vincent Morinière
Author: Audrey Pawtowski
Author: Christelle Arrondel
Author: Satu-Leena Sallinen
Author: Carola Saloranta
Author: Carol Clericuzio
Author: Géraldine Viot
Author: Julia Tantau
Author: Sophie Blesson
Author: Sylvie Cloarec
Author: Marie Christine Machet
Author: David Chitayat
Author: Christelle Thauvin
Author: Nicole Laurent
Author: Julian R. Sampson
Author: Jonathan A Bernstein
Author: Alix Clemenson
Author: Fabienne Prieur
Author: Laurent Daniel
Author: Annie Levy-Mozziconacci
Author: Katherine Lachlan
Author: Jean Luc Alessandri
Author: François Cartault
Author: Jean Pierre Rivière
Author: Nicole Picard
Author: Clarisse Baumann
Author: Anne Lise Delezoide
Author: Maria Belar Ortega
Author: Nicolas Chassaing
Author: Philippe Labrune
Author: Sui Yu
Author: Helen Firth
Author: Diana Wellesley
Author: Martin Bitzan
Author: Ahmed Alfares
Author: Nancy Braverman
Author: Lotte Krogh
Author: John Tolmie
Author: Harald Gaspar
Author: Bérénice Doray
Author: Silvia Majore
Author: Dominique Bonneau
Author: Stéphane Triau
Author: Chantal Loirat
Author: Albert David
Author: Deborah Bartholdi
Author: Amir Peleg
Author: Damien Brackman
Author: Rosario Stone
Author: Ralph DeBerardinis
Author: Pierre Corvol
Author: Annie Michaud
Author: Corinne Antignac
Author: Marie Claire Gubler

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