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

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

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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 allow genetic counseling and early prenatal diagnosis.

Original languageEnglish (US)
Pages (from-to)316-326
Number of pages11
JournalHuman mutation
Issue number2
StatePublished - Feb 2012


  • ACE
  • AGT
  • AGTR1
  • REN
  • Renal tubular dysgenesis
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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