title: Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis.
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 allow genetic counseling and early prenatal diagnosis.
authors.affiliation: Inserm U983, Faculté de Médecine Paris Descartes, Université Paris Descartes, Paris, France. olivier.gribouval@inserm.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Gribouval
authors.forename: Vincent
authors.initials: V
authors.lastname: Morinière
authors.forename: Audrey
authors.initials: A
authors.lastname: Pawtowski
authors.forename: Christelle
authors.initials: C
authors.lastname: Arrondel
authors.forename: Satu-Leena
authors.initials: SL
authors.lastname: Sallinen
authors.forename: Carola
authors.initials: C
authors.lastname: Saloranta
authors.forename: Carol
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authors.lastname: Clericuzio
authors.forename: Géraldine
authors.initials: G
authors.lastname: Viot
authors.forename: Julia
authors.initials: J
authors.lastname: Tantau
authors.forename: Sophie
authors.initials: S
authors.lastname: Blesson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cloarec
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Machet
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Christelle
authors.initials: C
authors.lastname: Thauvin
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: Alix
authors.initials: A
authors.lastname: Clemenson
authors.forename: Fabienne
authors.initials: F
authors.lastname: Prieur
authors.forename: Laurent
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authors.lastname: Daniel
authors.forename: Annie
authors.initials: A
authors.lastname: Levy-Mozziconacci
authors.forename: Katherine
authors.initials: K
authors.lastname: Lachlan
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Alessandri
authors.forename: François
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authors.lastname: Cartault
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Rivière
authors.forename: Nicole
authors.initials: N
authors.lastname: Picard
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.forename: Anne Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Maria
authors.initials: M
authors.lastname: Belar Ortega
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Philippe
authors.initials: P
authors.lastname: Labrune
authors.forename: Sui
authors.initials: S
authors.lastname: Yu
authors.forename: Helen
authors.initials: H
authors.lastname: Firth
authors.forename: Diana
authors.initials: D
authors.lastname: Wellesley
authors.forename: Martin
authors.initials: M
authors.lastname: Bitzan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Alfares
authors.forename: Nancy
authors.initials: N
authors.lastname: Braverman
authors.forename: Lotte
authors.initials: L
authors.lastname: Krogh
authors.forename: John
authors.initials: J
authors.lastname: Tolmie
authors.forename: Harald
authors.initials: H
authors.lastname: Gaspar
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Silvia
authors.initials: S
authors.lastname: Majore
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Triau
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Deborah
authors.initials: D
authors.lastname: Bartholdi
authors.forename: Amir
authors.initials: A
authors.lastname: Peleg
authors.forename: Damien
authors.initials: D
authors.lastname: Brackman
authors.forename: Rosario
authors.initials: R
authors.lastname: Stone
authors.forename: Ralph
authors.initials: R
authors.lastname: DeBerardinis
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Annie
authors.initials: A
authors.lastname: Michaud
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Gubler
mesh_terms: D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000002:abnormalities; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin