Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.
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.
Gribouval
Olivier
O
Inserm U574, Hôpital Necker-Enfants Malades, Université René Descartes, 149 rue de Sèvres, 75743 Paris cedex 15, France.
Gonzales
Marie
M
Neuhaus
Thomas
T
Aziza
Jacqueline
J
Bieth
Eric
E
Laurent
Nicole
N
Bouton
Jean Marie
JM
Feuillet
François
F
Makni
Saloua
S
Ben Amar
Hatem
H
Laube
Guido
G
Delezoide
Anne-Lise
AL
Bouvier
Raymonde
R
Dijoud
Frédérique
F
Ollagnon-Roman
Elisabeth
E
Roume
Joelle
J
Joubert
Madeleine
M
Antignac
Corinne
C
Gubler
Marie Claire
MC
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
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin