A common RET variant is associated with reduced newborn kidney size and function

Zhang, Zhao, Quinlan, Jackie, Hoy, Wendy, Hughson, Michael D., Lemire, Mathieu, Hudson, Thomas, Hueber, Pierre-Alain, Benjamin, Alice, Roy, Anne, Pascuet, Elena, Goodyer, Meigan, Raju, Chandhana, Houghton, Fiona, Bertram, John and Goodyer, Paul (2008) A common RET variant is associated with reduced newborn kidney size and function. Journal of the American Society of Nephrology, 19 10: 2027-2034. doi:10.1681/ASN.2007101098

Author Zhang, Zhao
Quinlan, Jackie
Hoy, Wendy
Hughson, Michael D.
Lemire, Mathieu
Hudson, Thomas
Hueber, Pierre-Alain
Benjamin, Alice
Roy, Anne
Pascuet, Elena
Goodyer, Meigan
Raju, Chandhana
Houghton, Fiona
Bertram, John
Goodyer, Paul
Title A common RET variant is associated with reduced newborn kidney size and function
Formatted title
A common RET variant is associated with reduced newborn kidney size and function
Journal name Journal of the American Society of Nephrology   Check publisher's open access policy
ISSN 1046-6673
Publication date 2008-10
Year available 2008
Sub-type Article (original research)
DOI 10.1681/ASN.2007101098
Volume 19
Issue 10
Start page 2027
End page 2034
Total pages 8
Editor B. O'Brien
Place of publication Washington, D.C., U.S.A.
Publisher American Society of Nephrology
Collection year 2009
Language eng
Subject C1
110311 Medical Genetics (excl. Cancer Genetics)
110312 Nephrology and Urology
1103 Clinical Sciences
Formatted abstract
Congenital nephron number varies five-fold among normal humans, and individuals at the lower end of this range may have an increased lifetime risk for essential hypertension or renal insufficiency; however, the mechanisms that determine nephron number are unknown. This study tested the hypothesis that common hypomorphic variants of the RET gene, which encodes a tyrosine kinase receptor critical for renal branching morphogenesis, might account for subtle renal hypoplasia in some normal newborns. A common single-nucleotide polymorphism (rs1800860 G/A) was identified within an exonic splicing enhancer in exon 7. The adenosine variant at mRNA position 1476 reduced affinity for spliceosome proteins, enhanced the likelihood of aberrant mRNA splicing, and diminished the level of functional transcript in human cells. In vivo, normal white newborns with an rs1800860(1476A) allele had kidney volumes 10% smaller and cord blood cystatin C levels 9% higher than those with the rs1800860(1476G) allele. These findings suggest that the RET(1476A) allele, in combination with other common polymorphic developmental genes, may account for subtle renal hypoplasia in a significant proportion of the white population. Whether this gene variant affects clinical outcomes requires further study.
Copyright © 2008 by the American Society of Nephrology
Keyword RET variant
Reduced newborn kidney size
Mutant mice
Nephron endowment
Renal hypoplasia
Enteric neurons
PAX2 gene
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Wed, 08 Apr 2009, 16:07:17 EST by Amy Wong on behalf of Medicine - Royal Brisbane and Women's Hospital