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Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden
Stellan Mörner1, Pascale Richard, Elsadig Kazzam
1Department of Medicine, University Hospital, Umeå, Sweden. stellan.morner@medicin.umu.se
Insights
This study identified 11 mutations, including six novel ones, in sarcomeric protein genes causing hypertrophic cardiomyopathy (HCM) in northern Sweden. Myosin-binding protein C gene mutations were most common, often leading to later disease onset.
Area of Science:
- Genetics
- Cardiology
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disease.
- Mutations in sarcomeric protein genes are a common cause of HCM.
- Understanding genotype-phenotype correlations is crucial for diagnosis and management.
Purpose of the Study:
- To investigate the genetic basis of HCM in northern Sweden.
- To identify specific mutations in sarcomeric protein genes associated with HCM.
- To correlate identified genotypes with clinical phenotypes.
Main Methods:
- Mutation analysis of eight key sarcomeric protein genes in 46 unrelated individuals with HCM.
- Genes analyzed include beta-myosin heavy chain, myosin-binding protein C, troponin T, alpha-tropomyosin, myosin light chains, troponin I, and alpha-actin.
- Genotyping was performed on familial and sporadic HCM cases.
Main Results:
- Eleven mutations were identified in 13 individuals, with six being novel.
- Myosin-binding protein C gene mutations were the most prevalent (7 mutations).
- Beta-myosin heavy chain gene mutations were less frequent than previously reported; troponin I and regulatory myosin light chain genes had one mutation each.
Conclusions:
- This is the first genetic study of HCM in a Swedish population.
- Myosin-binding protein C gene mutations are the most common cause of HCM in northern Sweden.
- HCM associated with myosin-binding protein C mutations may present with later onset, necessitating consideration in clinical evaluations, especially in young adults with incomplete penetrance.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a heterogenous disease, with variable genotypic and phenotypic expressions, often caused by mutations in sarcomeric protein genes. The aim of this study was to identify the genotypes and associated phenotypes related to HCM in northern Sweden. In 46 unrelated individuals with familial or sporadic HCM, mutation analysis of eight sarcomeric protein genes was performed; the cardiac beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin T, alpha-tropomyosin, cardiac essential and regulatory myosin light chains, cardiac troponin I and cardiac alpha-actin. A total of 11 mutations, of which six were novel ones, were found in 13 individuals. Seven mutations were located in the myosin-binding protein C gene, two in the beta-myosin heavy chain gene and one in the regulatory myosin light chain and troponin I genes, respectively. This is the first Swedish study, where a population with HCM has been genotyped. Mutations in the cardiac myosin-binding protein C gene were the most common ones found in northern Sweden, whereas mutations in the beta-myosin heavy chain gene were less frequent than previously described. There are differences in the phenotypes mediated by these genes characterised by a more late-onset disease for the myosin-binding protein C gene mutations. This should be taken into consideration, when evaluating clinical findings in the diagnosis of the disease, especially in young adults in families with HCM, where penetrance can be expected to be incomplete in the presence of a myosin-binding protein C gene mutation.