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J Med Genet 41:e10 doi:10.1136/jmg.2003.010447
  • Online mutation report

Clinical and genetic characteristics of α cardiac actin gene mutations in hypertrophic cardiomyopathy

  1. J Mogensen1,2,
  2. A Perrot3,
  3. P S Andersen4,
  4. O Havndrup5,
  5. I C Klausen1,
  6. M Christiansen4,
  7. P Bross2,
  8. H Egeblad1,
  9. H Bundgaard5,
  10. K J Osterziel3,
  11. G Haltern6,
  12. H Lapp6,
  13. P Reinecke7,
  14. N Gregersen2,
  15. A D Børglum8
  1. 1Department of Cardiology, Skejby University Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
  2. 2Research Unit for Molecular Medicine, Skejby University Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
  3. 3Charité/Franz-Volhard-Klinik, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
  4. 4Department of Clinical Biochemistry, Statens Serum Institut Copenhagen, DK-2300 Copenhagen S, Denmark
  5. 5Department of Medicine B 2141, Heart Center, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark
  6. 6Heart Center Wuppertal, University Witten/Herdecke, 42283 Wuppertal, Germany
  7. 7Institute of Pathology, Heinrich Heine University, 40225 Düsseldorf, Germany
  8. 8Danish Center for Human Genome Research, Institute of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark
  1. Correspondence to:
 Dr J Mogensen
 Department of Cardiology, Skejby University Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark; jens.mogensendadlnet.dk
  • Received 11 May 2003
  • Accepted 10 June 2003

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.

MATERIALS AND METHODS

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 …