Whole-Exome Sequencing Reveals GATA4 and PTEN Mutations as a Potential Digenic Cause of Left Ventricular Noncompaction
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
A 48-year-old male proband presented with atypical chest pain. An echocardiogram revealed possible left ventricular apical noncompaction that was confirmed by cardiac magnetic resonance imaging as left ventricular noncompaction cardiomyopathy (LVNC; Figure 1A). His ejection fraction was initially preserved at 60% but declined to 45% over the subsequent 6 years despite optimal medical therapy. His asymptomatic 19-year-old son was diagnosed with LVNC at the time of a screening echocardiogram, and follow-up cardiac magnetic resonance imaging confirmed the diagnosis (Figure 1B). His ejection fraction was 50% at the time of diagnosis and was subsequently stable for 5 years with medical therapy. An echocardiogram from the proband’s father showed normal left ventricular structure and function with no excess trabeculation (Figure 1C and 1D). The proband’s daughter had a normal echocardiogram. There were no other family members with a known history of cardiomyopathy or heart failure (Figure 1E).
A standard dilated cardiomyopathy panel genetic test (27 genes) on a sample from the proband revealed no pathogenic mutations. Whole-exome sequencing was then performed for the proband, his parents, and his son. Analysis of whole-exome sequencing demonstrated 2 variants that were considered to be potentially causative. The first, GATA4 c.778 C>T, Arg260Trp, was present in the proband, his son, and his unaffected father (Figure 1E). The …