Abstract
Congenital heart disease (CHD) is one of the most common birth defects, and recent studies indicate cilia-related mutations play a central role in the genetic etiology of CHD. As cilia are also known to have important roles in kidney development and disease, it is not surprising that renal anomalies were found to be enriched among CHD mutant mice recovered in a large-scale mouse forward genetic screen. Indeed 42% of mutations identified to cause both CHD and renal anomalies were cilia-related. Many of these cilia mutations comprise cilia transition zone or inversin compartment components, consistent with the known role of these cilia proteins in a wide variety of ciliopathies. The high prevalence of CHD with congenital anomalies of the kidney and urinary tract (CAKUT) observed in mice was also corroborated with clinical studies that showed 20–30% of CHD patients have renal anomalies. Together these findings suggest CHD patients may benefit from early screening for renal anomalies to allow early diagnosis and intervention to improve outcome for this vulnerable patient population.
Highlights
Reviewed by: Kathryn Hentges, University of Manchester, United Kingdom Claudio Cortes, UMR7288 Institut de Biologie du Développement de Marseille (IBDM), France
As cilia mutations are well-described in the context of CAKUT, this would suggest cilia defects may have a central role in mediating both Congenital heart disease (CHD) and CAKUT phenotypes
Together these findings suggest the routine evaluation of CHD patients for renal anomalies with simple non-invasive renal ultrasound may be warranted. This may allow early diagnosis and early therapeutic intervention to treat and manage any renal dysfunction that could negatively impact the long-term outcome of this high-risk patient population. Studies in both CHD mutant mice and CHD patients showed CAKUT is highly associated with CHD
Summary
Reviewed by: Kathryn Hentges, University of Manchester, United Kingdom Claudio Cortes, UMR7288 Institut de Biologie du Développement de Marseille (IBDM), France. Congenital heart disease (CHD) is one of the most common birth defects, and recent studies indicate cilia-related mutations play a central role in the genetic etiology of CHD. These findings suggest an overlapping genetic etiology for CHD and CAKUT Consistent with this is the fact that several previously reported mouse models (not individually discussed in this review) have found genetic disruption of a single gene can affect both heart and kidney development, and that many genetic syndromes can present with both cardiac and renal anomalies [6,7,8,9]. Insights into the genetic etiology of CHD may help elucidate the etiology of CAKUT Relevant to this is the recent unexpected finding from a large-scale forward genetic screen in mice indicating a significant role for cilia-related mutations in the pathogenesis of CHD [10]. We briefly discuss CAKUT and its association with CHD, and its shared genetic etiology involving cilia-related mutations
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