by Laura Daniel
Hypoplastic left heart syndrome (HLHS) affects one of every 4,344 newborns. It has high morbidity and mortality but little is known about the pathogenesis.
In a recent paper published in Pediatric Cardiology, Charles C. Hong, M.D., Ph.D., and colleagues report that mutations in the gene NOTCH1 might be a cause.
Newborns with HLHS have a severely underdeveloped left ventricle and without treatment the condition is fatal. Treatment often includes cardiac transplant; therefore, discovering the cause could allow the creation of alternative treatments.
Using whole exome sequencing, Hong reported that a nonsense mutation in NOTCH1, which results in a severe truncated Notch1 transmembrane receptor, was the likely cause of HLHS and another heart condition – hypoplastic right heart syndrome – in one family.
Notch1 controls cell fate and has been implicated in various types of structural heart disease. The findings, which suggest that HLHS is caused by a defect in the aortic outflow tract rather than ventricular morphogenesis, could eventually lead to new treatments for the condition.
The study was supported in part by National Institutes of Health grants HL104040, GM118557, HD068256 and TR000445.
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