title: Genetic link between renal birth defects and congenital heart disease.
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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213 373 Plantation Street Worcester, Massachusetts 01605, USA.
authors.forename: Jovenal T
authors.initials: JT
authors.lastname: San Agustin
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Klena
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Granath
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital Drive 45th Street and Penn Avenue Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Panigrahy
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital Drive 45th Street and Penn Avenue Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Stewart
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital Drive 45th Street and Penn Avenue Pittsburgh, Pennsylvania 15201, USA.
authors.forename: William
authors.initials: W
authors.lastname: Devine
authors.affiliation: Electron Microscopy Core, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Strittmatter
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Jonassen
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213 373 Plantation Street Worcester, Massachusetts 01605, USA.
authors.forename: Gregory J
authors.identifier: http://orcid.org/0000-0002-6285-8796
authors.initials: GJ
authors.lastname: Pazour
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics; D004195:Disease Models, Animal; D000069337:Fused Kidney / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D006869:Hydronephrosis / Q000235:genetics; D007668:Kidney / Q000002:abnormalities* / Q000166:cytology / Q000473:pathology; D007674:Kidney Diseases / Q000151:congenital / Q000235:genetics; D052177:Kidney Diseases, Cystic / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D014564:Urogenital Abnormalities / Q000235:genetics*; D014718:Vesico-Ureteral Reflux / Q000235:genetics