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Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations
  1. Paal Skytt Andersena,
  2. Ole Havndrupb,
  3. Henning Bundgaardb,
  4. Johanna Catharina Moolman-Smookc,
  5. Lars Allan Larsena,
  6. Jens Mogensend,
  7. Paul Andries Brinke,
  8. Anders Dupont Børglumf,
  9. Valerie Ann Corfieldc,
  10. Keld Kjeldsenb,
  11. Jens Vuusta,
  12. Michael Christiansena
  1. aDepartment of Clinical Biochemistry, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark, bDepartment of Medicine B, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, cUS/MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, University of Stellenbosch Medical School, Tygerberg, South Africa, dDepartment of Cardiology, Skejby University Hospital, Aarhus, Denmark, eDepartment of Internal Medicine, University of Stellenbosch Medical School and Tygerberg Hospital, Tygerberg, South Africa, fInstitute of Human Genetics, University of Aarhus, Aarhus, Denmark
  1. Dr Christiansen,mic{at}

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Editor—Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which may afflict as many as 1 in 500 subjects.1 The disease is characterised by an unexplained local or general myocardial hypertrophy and by myocyte disarray.2 Molecular genetic studies have so far identified nine disease associated genes, all of which encode sarcomeric proteins. The two genes in which most mutations have been described are the β-myosin heavy chain (MYH7)3 and the myosin binding protein C (MYBPC3) genes,4 each of which may account for up to 30% of all familial cases. Mutations in α-tropomyosin (TPM1),5troponin T (TNNT2),5 6troponin I (TNNI3),6 cardiac α-actin (ACTC),7 titin (TTN),8 and the essential (MYL3) and the regulatory (MYL2) myosin light chain genes have also been associated with FHC.9 This pronounced genetic heterogeneity may be the principal cause of the phenotypic variability that is seen in FHC. Thus, mutations inTNNT2 seem to be associated with sudden death at a young age,10 11 whereas families with mutations in MYBPC3 are generally characterised by progressive hypertrophy and a late onset of clinical manifestation.12 13 Furthermore, it has been proposed that a certain rare form of hypertrophic cardiomyopathy (HCM), asymmetric septal hypertrophy predominantly confined to the midventricular region, known as the midventricular hypertrophy (MVH) phenotype, may be associated with mutations in the two myosin light chain genes.9 However, limited and contradictory clinical information is available on FHC caused by mutations in these genes.9 14

We have studied MYL2 andMYL3 in 68 consecutively collected FHC families from Denmark and in 130 probands from South Africa. We established the frequency of myosin light chain mutations and assessed whether mutations in these two genes do cause a distinct …

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