Published Online
on July 24, 2009

A more recent version of this article appeared on October 1, 2009

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Original Article

Sarcomere Mutations in Cardiomyopathy with Left Ventricular Hypertrabeculation

Lisa M. Dellefave; Peter Pytel; Stephanie Mewborn; Bassem Mora; Deborah L. Guris; Savitri Fedson; Darrel Waggoner; Ivan Moskowitz and Elizabeth M. McNally¹

The University of Chicago, Chicago, IL

^* Corresponding author; email: emcnally{at}uchicago.edu

Background—Mutations in the genes encoding sarcomere proteins have been associated with both hypertrophic and dilated cardiomyopathy. Recently, mutations in myosin heavy chain (MYH7), cardiac actin (ACTC) and troponin T (TNNT2) were associated with left ventricular noncompaction, a form of cardiomyopathy characterized with hypertrabeculation that may also include reduced function of the left ventricle.

Methods and Results—We employed clinically-available genetic testing on three cases referred for evaluation of left ventricular dysfunction and noncompaction of the left ventricle and found that all three individuals carried sarcomere mutations. The first patient presented with neonatal heart failure and was referred for left ventricular noncompaction cardiomyopathy. Genetic testing found two different mutations in MYBPC3 in trans. The first mutation, 3776 del a, Q1259fs, rendered a frame shift at 1259 of cardiac myosin binding protein C and the second mutation was L1200P. The frameshift mutation was also found in this mother who displayed mild echocardiographic features of cardiomyopathy with only subtle increase in trabeculation and an absence of hypertrophy. A second pediatric patient presented with heart failure and was found to carry a de novo MYH7 R369Q mutation. The third case was an adult patient with dilated cardiomyopathy referred for ventricular hypertrabeculation. He had a family history of congestive heart failure, including pediatric onset cardiomyopathy where three individuals in the family were found to have the MYH7 mutation R1250W.

Conclusions—Genetic testing should be considered for cardiomyopathy with hypertrabeculation.

Key Words: cardiomyopathy • contractility • genetics • heart failure • myocardial contraction • gene mutation • myosin binding protein C • myosin heavy chain • sarcomere