TY - JOUR T1 - Clinical and genetic characteristics of α cardiac actin gene mutations in hypertrophic cardiomyopathy JF - Journal of Medical Genetics JO - J Med Genet SP - e10 LP - e10 DO - 10.1136/jmg.2003.010447 VL - 41 IS - 1 AU - J Mogensen AU - A Perrot AU - P S Andersen AU - O Havndrup AU - I C Klausen AU - M Christiansen AU - P Bross AU - H Egeblad AU - H Bundgaard AU - K J Osterziel AU - G Haltern AU - H Lapp AU - P Reinecke AU - N Gregersen AU - A D Børglum Y1 - 2004/01/01 UR - http://jmg.bmj.com/content/41/1/e10.abstract N2 - Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease defined by unexplained myocardial hypertrophy. The prevalence is about 0.2% in the general population. The condition is characterised by a heterogeneous disease expression, and common symptoms include angina, dyspnoea, palpitations, syncope, and exercise limitation. Hypertrophic cardiomyopathy is a frequent cause of sudden cardiac death in young people.1 More than 200 mutations associated with the disease have been identified in sarcomeric contractile protein genes: TNNT2 (troponin T), MYL3 (essential myosin light chain), MYBPC3 (myosin binding protein C), MYL2 (regulatory myosin light chain), MYH7 (β myosin heavy chain), TPM1 (α tropomyosin), ACTC (α cardiac actin), and TNNI3 (troponin I).2–4 In addition, mutations recently have been reported in two non-sarcomeric genes.5–7 Mutations in ACTC have also been reported to cause the inherited form of idiopathic dilated cardiomyopathy (DCM). It has been suggested previously that ACTC mutations that affect sarcomere contraction lead to HCM, whereas ACTC mutations that affect force transmission from the sarcomere to the surrounding syncytium lead to DCM.3,8 We report the clinical and genetic characteristics of ACTC mutations in 206 consecutive patients with HCM. Informed consent was obtained from each participant in accordance with local institutional review committee guidelines. We investigated 206 consecutive Caucasian probands with HCM from Germany (n = 146) or Denmark (n = 60) by mutation analysis of ACTC. We physically and genetically investigated relatives of probands who carried ACTC mutations. The diagnosis of HCM was based on the presence of unexplained myocardial hypertrophy.3,9,10 In brief, a person was defined as having HCM if the maximal left ventricular wall thickness by echocardiography or cardiac magnetic resonance scan was ⩾13 mm or the electrocardiogram (ECG) showed major Q wave abnormalities, left ventricular hypertrophy, or marked repolarisation alterations. One patient (pedigree B, participant I-1) was … ER -