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Genetics of congenital anomalies of the kidney and urinary tract

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Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 1 in 500 births and are a major cause of morbidity in children. Notably, CAKUT account for the most cases of pediatric end-stage renal disease and predispose the individual to hypertension and cardiovascular disease throughout life. Although some forms of CAKUT are a part of a syndrome or are associated with a positive family history, most cases of renal system anomalies are sporadic and isolated to the urinary tract. Broad phenotypic spectrum of CAKUT and variability in genotype–phenotype correlation indicate that pathogenesis of CAKUT is a complex process that depends on interplay of many factors. This review focuses on the genetic mechanisms (single-gene mutations, modifier genes) leading to renal system anomalies in humans and discusses emerging insights into the role of epigenetics, in utero environmental factors, and micro-RNAs (miRNAs) in the pathogenesis of CAKUT. Common gene networks that function in defined temporospatial fashion to orchestrate renal system morphogenesis are highlighted. Derangements in cellular, molecular, and morphogenetic mechanisms that direct normal renal system development are emphasized as a major cause of CAKUT. Integrated understanding of how morphogenetic process disruptions are linked to CAKUT will enable improved diagnosis, treatment, and prevention of congenital renal system anomalies and their consequences.

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Authors and Affiliations

  1. Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA

    Renfang Song & Ihor V. Yosypiv

  2. Department of Pediatrics, SL-37, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    Ihor V. Yosypiv

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  1. Renfang Song
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  2. Ihor V. Yosypiv
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Correspondence to Ihor V. Yosypiv.

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Supplemental Table 1

Multiorgan syndromes associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans (DOC 64.5 kb)

Supplemental Table 2

Glossary of genes (DOC 56.5 kb)

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Song, R., Yosypiv, I.V. Genetics of congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 26, 353–364 (2011). https://doi.org/10.1007/s00467-010-1629-4

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