Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis

Nat Genet. 2005 Sep;37(9):964-8. doi: 10.1038/ng1623. Epub 2005 Aug 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiotensinogen / genetics
  • Anuria / etiology*
  • Family
  • Female
  • Genes, Recessive*
  • Heterozygote
  • Homozygote
  • Humans
  • Infant, Newborn
  • Kidney Tubules / abnormalities*
  • Kidney Tubules / pathology
  • Male
  • Mutation / genetics*
  • Peptidyl-Dipeptidase A / genetics
  • Pregnancy
  • Receptor, Angiotensin, Type 1 / genetics
  • Renin / genetics


  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Peptidyl-Dipeptidase A
  • Renin