Renal Aplasia in Humans Is Associated with RET Mutations

Michael A. Skinner, Shawn D. Safford, Justin G. Reeves, Margaret E. Jackson, Alex J. Freemerman

Research output: Contribution to journalArticle

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Abstract

In animal models, kidney formation is known to be controlled by the proteins RET, GDNF, and GFRA1; however, no human studies to date have shown an association between abnormal kidney development and mutation of these genes. We hypothesized that stillborn fetuses with congenital renal agenesis or severe dysplasia would possess mutations in RET, GDNF, or GFRA1. We assayed for mutations in these genes in 33 stillborn fetuses that had bilateral or unilateral renal agenesis (29 subjects) or severe congenital renal dysplasia (4 subjects). Mutations in RET were found in 7 of 19 fetuses with bilateral renal agenesis (37%) and 2 of 10 fetuses (20%) with unilateral agenesis. In two fetuses, there were two different RET mutations found, and a total of ten different sequence variations were identified. We also investigated whether these mutations affected RET activation; in each case, RET phosphorylation was either absent or constitutively activated. A GNDF mutation was identified in only one fetus with unilateral agenesis; this subject also had two RET mutations. No GFRA1 mutations were seen in any fetuses. These data suggest that in humans, mutations in RET and GDNF may contribute significantly to abnormal kidney development.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalAmerican Journal of Human Genetics
Volume82
Issue number2
DOIs
StatePublished - Feb 8 2008

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Mutation
Fetus
Glial Cell Line-Derived Neurotrophic Factor
Kidney
Renal Adysplasia
Genes
Animal Models
Phosphorylation
Hereditary renal agenesis
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Skinner, M. A., Safford, S. D., Reeves, J. G., Jackson, M. E., & Freemerman, A. J. (2008). Renal Aplasia in Humans Is Associated with RET Mutations. American Journal of Human Genetics, 82(2), 344-351. https://doi.org/10.1016/j.ajhg.2007.10.008

Renal Aplasia in Humans Is Associated with RET Mutations. / Skinner, Michael A.; Safford, Shawn D.; Reeves, Justin G.; Jackson, Margaret E.; Freemerman, Alex J.

In: American Journal of Human Genetics, Vol. 82, No. 2, 08.02.2008, p. 344-351.

Research output: Contribution to journalArticle

Skinner, MA, Safford, SD, Reeves, JG, Jackson, ME & Freemerman, AJ 2008, 'Renal Aplasia in Humans Is Associated with RET Mutations', American Journal of Human Genetics, vol. 82, no. 2, pp. 344-351. https://doi.org/10.1016/j.ajhg.2007.10.008
Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ. Renal Aplasia in Humans Is Associated with RET Mutations. American Journal of Human Genetics. 2008 Feb 8;82(2):344-351. https://doi.org/10.1016/j.ajhg.2007.10.008
Skinner, Michael A. ; Safford, Shawn D. ; Reeves, Justin G. ; Jackson, Margaret E. ; Freemerman, Alex J. / Renal Aplasia in Humans Is Associated with RET Mutations. In: American Journal of Human Genetics. 2008 ; Vol. 82, No. 2. pp. 344-351.
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