title: Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.
abstract: Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development.
authors.affiliation: Inserm U574, Hôpital Necker-Enfants Malades, Université René Descartes, 149 rue de Sèvres, 75743 Paris cedex 15, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gribouval
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuhaus
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Aziza
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Bouton
authors.forename: François
authors.initials: F
authors.lastname: Feuillet
authors.forename: Saloua
authors.initials: S
authors.lastname: Makni
authors.forename: Hatem
authors.initials: H
authors.lastname: Ben Amar
authors.forename: Guido
authors.initials: G
authors.lastname: Laube
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dijoud
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ollagnon-Roman
authors.forename: Joelle
authors.initials: J
authors.lastname: Roume
authors.forename: Madeleine
authors.initials: M
authors.lastname: Joubert
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Gubler
mesh_terms: D000293:Adolescent; D000808:Angiotensinogen / Q000235:genetics; D001002:Anuria / Q000209:etiology*; D005190:Family; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007684:Kidney Tubules / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012083:Renin / Q000235:genetics
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin