Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Apr;29(4):695-704.
doi: 10.1007/s00467-013-2684-4. Epub 2014 Jan 8.

Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans

Asaf Vivante  1 , Stefan Kohl, Daw-Yang Hwang, Gabriel C Dworschak, Friedhelm Hildebrandt
Affiliations
Review

Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans

Asaf Vivante et al. Pediatr Nephrol. 2014 Apr.

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40-50 % of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently, only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single-gene causes of CAKUT and their developmental origin. Currently, more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Mechanisms of kidney development and corresponding CAKUT-causing genes in mice and humans
Steps of nephrogenesis (left column, a to d) and the corresponding CAKUT-causing genes in mice (orange column) and human (right yellow column). The kidney is formed via reciprocal induction between the ureteric bud (UB) and the metanephric mesenchyme (MM) (a). The UB invades the MM cells, which in turn condense around the tip of the branching UB (pre-tubular aggregate). Polarized renal vesicles subsequently develop in mesenchyme-to-epithelial transition (MET) (b). The cells sequentially form comma-shaped and S-shaped bodies and finally give rise to the mature nephron segments (distal and proximal tubule, loop of Henle, and glomerulus) (d). At the same time, the uretric bud branches in a highly reproducible manner and nephrons are induced at each ureteric bud tip (c). These branches eventually form the collecting system, including collecting ducts, renal pelvis, ureter and bladder trigone. WD Wolffian duct; UB ureteric bud; MM matanephrogenic mesenchyme; CD collecting duct; DT distal tubule; PT proximal tubule.
See this image and copyright information in PMC

References

    1. Schedl A. Renal abnormalities and their developmental origin. Nature Reviews Genetics. 2007;8:791–802. - PubMed
    1. (2008) North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2008 Annual report. Rockville, MD: The EMMES Corporation; 2008.
    1. Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont ME, Sullivan MJ, Dobyns WB, Eccles MR. Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet. 1995;9:358–364. - PubMed
    1. Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI, Sovik O. A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Human molecular genetics. 1999;8:2001–2008. - PubMed
    1. Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Weil D, Cruaud C, Sahly I, Leibovici M, Bitner-Glindzicz M, Francis M, Lacombe D, Vigneron J, Charachon R, Boven K, Bedbeder P, Van Regemorter N, Weissenbach J, Petit C. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet. 1997;15:157–164. - PubMed

Publication types

LinkOut - more resources