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

Abstract

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.

• Authors: Camille Humbert, Flora Silbermann, Bharti Morar, Mélanie Parisot, Mohammed Zarhrate, Cécile Masson, Frédéric Tores, Patricia Blanchet, Marie-José Perez, Yuliya Petrov, Philippe Khau Van Kien, Joelle Roume, Brigitte Leroy, Olivier Gribouval, Luba Kalaydjieva, Laurence Heidet, Rémi Salomon, Corinne Antignac, Alexandre Benmerah, Sophie Saunier, Cécile Jeanpierre
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 94 Issue 2 Pg. 288-94 (Feb 06 2014) ISSN: 1537-6605 [Electronic] United States
• PMID: 24439109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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