Vasile et al. (2006) studied a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy, who presented with congestive heart failure and moderate (New York Heart Association class III) symptoms of exertional dyspnea. Echocardiogram showed a hyperdynamic left ventricle ... Vasile et al. (2006) studied a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy, who presented with congestive heart failure and moderate (New York Heart Association class III) symptoms of exertional dyspnea. Echocardiogram showed a hyperdynamic left ventricle with an ejection fraction of 85%, systolic midcavity obliteration, and prominent hypertrophy involving the midventricle, septum, and the apex. Concentric severe hypertrophy was localized at the apex, with the ventricular wall measuring approximately 16 mm at the basal septum, increasing to 22 mm at the midventricle, and increasing further at the apex. There was no left ventricular outflow tract obstruction. She had mild pulmonary hypertension, with a pulmonary artery systolic pressure of 48 mm Hg. Her family history was positive for sudden cardiac death involving an uncle. Histologic examination of an apical myectomy specimen confirmed the typical microscopic features of CMH, including diffuse myocyte hypertrophy, focal myocyte disarray, focal interstitial fibrosis, and endocardial fibrosis. Ultrastructural analysis showed no storage vesicles or ultrastructural mitochondrial abnormalities. Immunostaining revealed normal staining of the Z-lines but markedly reduced vinculin/metavinculin staining in the intercalated discs. Vasile et al. (2006) described a 76-year-old Caucasian woman who presented with congestive heart failure and mild (NYHA class II) symptoms of progressive exertional dyspnea, whose echocardiogram revealed basal septal hypertrophy and a sigmoidal contoured septum having a maximal septal wall thickness of 18 to 20 mm. There was severe left ventricular outflow tract obstruction, with a maximum instantaneous gradient exceeding 100 mm Hg. The patient underwent extended left ventricular septal myomectomy due to symptoms refractory to pharmacotherapy. Histologic examination of the specimen showed the characteristic features of CMH, including myocyte hypertrophy and disarray and focal interstitial fibrosis; immunostaining showed normal Z-line staining but markedly reduced vinculin/metavinculin staining in the intercalated discs.
In a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy, who was negative for mutation in 8 known CMH-associated sarcomere/myofilament-encoding genes, Vasile et al. (2006) identified a heterozygous mutation in the VCL gene (R975W; 193065.0002). The same mutation ... In a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy, who was negative for mutation in 8 known CMH-associated sarcomere/myofilament-encoding genes, Vasile et al. (2006) identified a heterozygous mutation in the VCL gene (R975W; 193065.0002). The same mutation had previously been identified in a patient with dilated cardiomyopathy (see CMD1W; 611407). In a cohort of 228 CMH patients who were negative for mutation in 12 known CMH-associated sarcomere/myofilament-encoding genes, Vasile et al. (2006) analyzed all 22 exons of the VCL gene and identified a heterozygous mutation in a 76-year-old Caucasian woman (L277M; 193065.0003).