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Hypoplastic Left Heart Syndrome (HLHS) is a life-threatening congenital heart defect with unknown etiology. Here we hypothesize that HLHS has etiologic roots in maternal asymptomatic coxsackievirus B infection. Coxsackievirus has been demonstrated to disrupt normal distribution of small ubiquitin-like modifiers (SUMO) in the cell. The vital cardiac transcription factor, Nkx2-5, has been shown to be dependent on SUMOylation for proper function. Specifically, co-localization of SUMO and Nkx2.5 has been identified, as well as decreased SUMOylation associated with Nkx2-5 mutants. As Nxk2-5 is essential for fetal heart development and mutations in the gene for this vital transcription factor have been linked to HLHS, disruption of the regular SUMOylation patterns of Nkx2-5 may have severe consequences on cardiac development. Considering this evidence, we propose a novel mechanism for the underlying cause of HLHS. Specifically, we propose that asymptomatic maternal coxsackievirus infection crosses the placental barrier and disrupts SUMOylation processes during fetal development. This, in turn alters the function of Nkx2-5, ultimately leading to underdevelopment of the fetal heart and cardiac anomalies such as Hypoplastic Left Heart Syndrome.

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Hypoplastic Left Heart Syndrome; Congenital heart disease; Coxsackievirus infections; Small Ubiquitin-Related Modifier Proteins


Cardiovascular Diseases | Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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Conference Proceeding

Maternal Coxsackievirus B Induced Dysregulation of SUMOylation Processes as a Potential Cause of Hypoplastic Left Heart Syndrome