1. ¹Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark
2. ²Department of Medicine B, Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3. ³Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark
4. ⁴Copenhagen Heart Arrhythmia Research Centre, Copenhagen, Denmark

Correspondence: Dr P Skytt Andersen, Department of Clinical Biochemistry, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Tel: +45 32683665; Fax: +45 32683878; E-mail: psa@ssi.dk

Received 26 May 2004; Revised 31 August 2004; Accepted 1 September 2004; Published online 13 October 2004.

Abstract

Familial hypertrophic cardiomyopathy (FHC) is, in most cases, a disease of the sarcomere, caused by a mutation in one of 10 known sarcomere disease genes. More than 266 mutations have been identified since 1989. The FHC disease gene first characterized MYH7, encodes the cardiac -myosin heavy chain, and contains more than 115 of these mutations. However, in most studies, only the region encoding the globular head and the hinge region of the mature cardiac -myosin heavy chain have been investigated. Furthermore, most studies carries out screening for mutations in the most prevalent disease genes, and discontinues screening when an apparent disease-associated mutation has been identified. The aim of the present study was to screen for mutations in the rod region of the MYH7 gene in all probands of the cohort, regardless of the known genetic status of the proband. Three disease-causing mutations were identified in the rod region in four probands using capillary electrophoresis single-strand conformation polymorphism as a screening method. All mutations were novel: N1327K, R1712W, and E1753K. Two of the probands had already been shown to carry other FHC-associated mutations. In conclusion, we show that in the Danish cohort we find one third of all MYH7 mutations in the rod-encoding region and we find that two of the patients carrying these mutations also carry mutations in other FHC disease genes stressing the need for a complete screening of all known disease genes in FHC-patients.