Genetic link between renal birth defects and congenital heart disease

Nat Commun. 2016 Mar 22:7:11103. doi: 10.1038/ncomms11103.

Abstract

Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Congenital Abnormalities / genetics
  • Disease Models, Animal
  • Fused Kidney / genetics
  • Heart Defects, Congenital / genetics*
  • Humans
  • Hydronephrosis / genetics
  • Kidney / abnormalities*
  • Kidney / cytology
  • Kidney / pathology
  • Kidney Diseases / congenital
  • Kidney Diseases / genetics
  • Kidney Diseases, Cystic / genetics
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Urogenital Abnormalities / genetics*
  • Vesico-Ureteral Reflux / genetics

Supplementary concepts

  • Hereditary renal agenesis