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A point mutation in exon 13 of the beta cardiac myosin heavy chain (MHC) gene is present in all individuals affected with familial hypertrophic cardiomyopathy (FHC) from a large kindred. This missense mutation converts a highly conserved arginine residue (Arg-403) to a glutamine. Affected individuals from an unrelated family lack this missense mutation, but(More)
We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha-tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC) linked to chromosome 15q2. These findings implicated components of the troponin complex as candidate genes at other FHC loci, particularly cardiac troponin T, which was mapped in this study to chromosome 1q. Missense(More)
Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by a ventricular hypertrophy predominantly affecting the interventricular septum and associated with a large extent of myocardial and myofibrillar disarray. It is the most common cause of sudden death in the young. In the four disease loci found, three genes have been(More)
Highly purified nicking-closing enzyme from mouse cells in 20-fold enzyme/substrate excess converts closed circular native PM2, ColE1, and Minicol DNA into limit product sets of DNAs. Each set has a mean degree of supercoiling of approximately zero. The individual species in the sets differ by deltatau = +/-1, +/-2, etc., and the relative masses fit a(More)
BACKGROUND Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere characterised clinically by myocardial hypertrophy and its consequences. Phenotypic expression is heterogeneous even within families with the same aetiological mutation and may be influenced by additional genetic factors. OBJECTIVE To determine the influence of genetic(More)
The polymerase chain reaction (PCR) is a method for the selective amplification of DNA or RNA segments of up to 2 kilobase-pairs (kb) or more in length. Synthetic oligonucleotides flanking sequences of interest are used in repeated cycles of enzymatic primer extension in opposite and overlapping directions. The essential steps in each cycle are thermal(More)
AIMS Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes that encode sarcomeric proteins. In this study we investigated the involvement of the sarcomeric myosin binding protein C in the Dutch HCM population. METHODS AND RESULTS We initially screened 22 Dutch index patients for mutations in the MYBPC3 gene, which revealed four different(More)
OBJECTIVES We studied the clinical and genetic features of familial hypertrophic cardiomyopathy (FHC) caused by an Asp175Asn mutation in the alpha-tropomyosin gene in affected subjects from three unrelated families. BACKGROUND Correlation of genotype and phenotype has provided important information in FHC caused by beta-cardiac myosin and cardiac troponin(More)
Mutations causing familial hypertrophic cardiomyopathy (HCM) have been described in at least 11 genes encoding cardiac sarcomeric proteins. In this study, three previously unknown deletions have been identified in the human cardiac genes coding for beta-myosin heavy chain (MYH7 on chromosome 14) and myosin-binding protein-C (MYBPC3 on chromosome 11). In(More)
BACKGROUND Hypertrophic cardiomyopathy is a myocardial disorder resulting from inherited sarcomeric dysfunction. We report a mutation in the myosin-binding protein-C (MyBP-C) gene, its clinical consequences in a large family, and myocardial tissue findings that may provide insight into the mechanism of disease. METHODS AND RESULTS History and clinical(More)