Geier et al. (2008) reported the clinical characteristics of affected individuals from 5 CMH families with mutations in the CSRP3 gene, 3 of which had been previously studied by Geier et al. (2003). Most affected persons had pronounced ... Geier et al. (2008) reported the clinical characteristics of affected individuals from 5 CMH families with mutations in the CSRP3 gene, 3 of which had been previously studied by Geier et al. (2003). Most affected persons had pronounced hypertrophy and reported onset of symptoms in young adulthood. A history of sudden death was present in 2 families. Geier et al. (2008) observed considerable interindividual variability in the extent and localization of left ventricular hypertrophy: while most individuals with marked hypertrophy had asymmetric septal hypertrophy, 1 affected relative had severe apical hypertrophy, another had concentric, and another midventricular hypertrophy. Myocardial biopsy from the proband of a large German family previously studied by Geier et al. (2003) showed a histologic pattern typical for CMH, e.g., variably hypertrophied cardiomyocytes, myocyte disarray, and perivascular and interstitial fibrosis and scarring. Electron microscopy displayed typical nuclear pleomorphism with bizarre lobulated cardiomyocyte nuclei and no gross abnormalities of the sarcomere. Immunohistochemistry of a biopsy sample from this patient revealed areas of inhomogeneous and patchy muscle LIM protein (MLP) staining. - Skeletal Muscle Involvement Because MLP is expressed in both myocardium and in slow-twitch skeletal muscle, Geier et al. (2008) studied 5 CMH patients with CSRP3 mutations for skeletal muscle involvement. Three of the 5 patients complained of exertional myalgias and cramps and had moderately elevated creatine kinase levels. Skeletal muscle biopsies from the quadriceps or deltoid of 2 of the patients showed mild myopathic changes with cytoplasmic accumulation of amorphous material in a few fibers, changes considered typical for myofibrillar myopathy.
Geier et al. (2003) analyzed the CSRP3 gene in 200 patients with hypertrophic cardiomyopathy (CMH), 400 patients with dilated cardiomyopathy (CMD), and 500 controls, and identified 3 different mutations (600824.0002-600824.0004) that cosegregated with CMH in 3 unrelated families. ... Geier et al. (2003) analyzed the CSRP3 gene in 200 patients with hypertrophic cardiomyopathy (CMH), 400 patients with dilated cardiomyopathy (CMD), and 500 controls, and identified 3 different mutations (600824.0002-600824.0004) that cosegregated with CMH in 3 unrelated families. All known CMH disease genes were excluded in the largest family; no mutations were detected in the CMD patients or controls. The authors stated that all 3 probands had typical asymmetric septal hypertrophy; mutation-positive relatives in these families had mild symptoms and great variation in the extent of hypertrophy, although there was a history of sudden cardiac death in 2 of the 3 families. Geier et al. (2008) sequenced exons 2 and 3 of the CSRP3 gene in 652 CMD and 354 CMH patients and 533 unrelated controls and identified heterozygosity for a missense mutation in CSRP3 in 2 unrelated CMH probands (600824.0006).