Genetic, environmental, and epigenetic factors involved in CAKUT
Top Cited Papers
- 18 August 2015
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Nephrology
- Vol. 11 (12), 720-731
- https://doi.org/10.1038/nrneph.2015.140
Abstract
Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a spectrum of structural renal malformations and are the leading cause of end-stage renal disease in children. The genetic diagnosis of CAKUT has proven to be challenging due to genetic and phenotypic heterogeneity and incomplete genetic penetrance. Monogenic causes of CAKUT have been identified using different approaches, including single gene screening, and gene panel and whole exome sequencing. The majority of the identified mutations, however, lack substantial evidence to support a pathogenic role in CAKUT. Copy number variants or single nucleotide variants that are associated with CAKUT have also been identified. Numerous studies support the influence of epigenetic and environmental factors on kidney development and the natural history of CAKUT, suggesting that the pathogenesis of this syndrome is multifactorial. In this Review we describe the current knowledge regarding the genetic susceptibility underlying CAKUT and the approaches used to investigate the genetic basis of CAKUT. We outline the associated environmental risk factors and epigenetic influences on CAKUT and discuss the challenges and strategies used to fully address the involvement and interplay of these factors in the pathogenesis of the disease.Keywords
This publication has 130 references indexed in Scilit:
- Detection of Clinically Relevant Copy Number Variants with Whole-Exome SequencingHuman Mutation, 2013
- Phenotypic information in genomic variant databases enhances clinical care and research: The international standards for cytogenomic arrays consortium experienceHuman Mutation, 2012
- Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like SyndromeAmerican Journal of Human Genetics, 2011
- HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohortPediatric Nephrology, 2011
- Fetal environment, epigenetics, and pediatric renal diseasePediatric Nephrology, 2010
- Mutations in SOX17 are associated with congenital anomalies of the kidney and the urinary tractHuman Mutation, 2010
- LRP4 Mutations Alter Wnt/β-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz SyndromeAmerican Journal of Human Genetics, 2010
- FREM1 Mutations Cause Bifid Nose, Renal Agenesis, and Anorectal Malformations SyndromeAmerican Journal of Human Genetics, 2009
- Renal Aplasia in Humans Is Associated with RET MutationsAmerican Journal of Human Genetics, 2008
- Genetic approaches to human renal agenesis/hypoplasia and dysplasiaPediatric Nephrology, 2007