Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans

Am J Hum Genet. 2014 Feb 6;94(2):288-94. doi: 10.1016/j.ajhg.2013.12.017. Epub 2014 Jan 16.


Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Congenital Abnormalities / genetics*
  • Congenital Abnormalities / pathology
  • Female
  • Fetus / abnormalities
  • Genes, Recessive*
  • Homozygote
  • Humans
  • Integrin alpha Chains / genetics*
  • Integrin alpha Chains / metabolism
  • Kidney / abnormalities*
  • Kidney / pathology
  • Kidney Diseases / congenital*
  • Kidney Diseases / genetics
  • Kidney Diseases / pathology
  • Male
  • Mutation
  • Pedigree
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology


  • ITGA8 protein, human
  • Integrin alpha Chains
  • integrin alpha8

Supplementary concepts

  • Hereditary renal agenesis
  • Renal Adysplasia