Impact of next generation sequencing on our understanding of CAKUT

Semin Cell Dev Biol. 2019 Jul:91:104-110. doi: 10.1016/j.semcdb.2018.08.013. Epub 2018 Sep 5.


Congenital abnormalities of the kidney and urinary tract (CAKUT) form the leading cause of pediatric end-stage renal disease. Knowledge on the molecular mechanisms that underlie CAKUT leads to the improvement of DNA diagnostics and counseling regarding prognosis and recurrence risk estimation for CAKUT patients and their relatives. Implementation of next generation sequencing in research and diagnostic settings has led to the identification of the molecular basis of many developmental diseases. In this review, we summarize the efforts on next generation sequencing in CAKUT research and we discuss how next generation sequencing added to our understanding of CAKUT genetics. Although next generation sequencing has certainly proven to be a game changer in the field of disease gene identification and novel CAKUT-causing gene variants have been identified, most CAKUT cases still remain unsolved. Occurring with genetic and phenotypic heterogeneity along with incomplete penetrance, the identification of CAKUT etiology poses many challenges. We see great potential for combined -omics approaches that include next generation sequencing in the identification of CAKUT-specific biomarkers, which is necessary to optimize the care for CAKUT patients.

Keywords: CAKUT; Etiology; Genetics; Kidney disease; Next generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental*
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Kidney / embryology
  • Kidney / metabolism*
  • Kidney / pathology
  • Mutation*
  • Urogenital Abnormalities / diagnosis
  • Urogenital Abnormalities / embryology
  • Urogenital Abnormalities / genetics*
  • Vesico-Ureteral Reflux / diagnosis
  • Vesico-Ureteral Reflux / embryology
  • Vesico-Ureteral Reflux / genetics*

Supplementary concepts

  • Cakut