Integrin Alpha 8 Recessive Mutations Are Responsible for Bilateral Renal Agenesis in Humans
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- 作者：Camille Humbert ; Flora Silbermann ; Bharti Morar ; M茅lanie Parisot ; Mohammed Zarhrate ; C茅cile Masson ; Fr茅d茅ric Tores ; Patricia Blanchet ; Marie-Jos茅 Perez ; Yuliya Petrov ; Philippe Khau聽Van聽Kien ; Joelle Roume ; Brigitte Leroy ; Olivier Gribouval ; Luba Kalaydjieva ; Laurence Heidet ; R茅mi Salomon ; Corinne Antignac ; Alex ; re Benmerah ; Sophie Saunier ; C茅cile Jeanpierre ; et al.
- 刊名：The American Journal of Human Genetics
- 出版年：6 February, 2014
- 年：2014
- 卷：94
- 期：2
- 页码：288-294
- 全文大小：1180 K
文摘
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 伪8-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.