Genetic link between renal birth defects and congenital heart disease

• Published in: Nature communications Vol. 7; no. 1; p. 11103
• Main Authors: San Agustin, Jovenal T., Klena, Nikolai, Granath, Kristi, Panigrahy, Ashok, Stewart, Eileen, Devine, William, Strittmatter, Lara, Jonassen, Julie A., Liu, Xiaoqin, Lo, Cecilia W., Pazour, Gregory J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.03.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 14/19; 14/28; 14/63; 631/136; 631/208/2489/144; 631/443/592/75/1539; 64/60; 692/699/1585; Animals; Congenital Abnormalities - genetics; Disease Models, Animal; Fused Kidney - genetics; Heart Defects, Congenital - genetics; Humanities and Social Sciences; 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; multidisciplinary; Science; Science (multidisciplinary); Urogenital Abnormalities - genetics; Vesico-Ureteral Reflux - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11103

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. Using forward genetic screen in fetal mice, Gregory Pazour and colleagues describe mutants affecting kidney/urinary tract development. The authors also show that mutants that cause kidney defects overlaps with those leading to congenital heart defects, thus linking renal anomalies and congenital heart disease.