Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics
Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of...
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Institutionen för folkhälsa och klinisk medicin
2004
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ftumeauniv:oai:DiVA.org:umu-274 2023-10-09T21:54:31+02:00 Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics Mörner, Stellan 2004 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-274 eng eng Institutionen för folkhälsa och klinisk medicin Umeå University medical dissertations, 0346-6612 894 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-274 urn:isbn:91-7305-660-X info:eu-repo/semantics/openAccess Hypertrophic cardiomyopathy genetics autonomic nervous system familial amyloid polyneuropathy echocardiography Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2004 ftumeauniv 2023-09-22T13:52:11Z Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of this thesis was to identify the genotypes causing HCM in northern Sweden, to characterize the disease phenotypes and correlate these findings. Forty-six patients were recruited for the genetic studies (21 women), 11 familial and 35 sporadic cases. Eight sarcomeric protein genes were screened for mutations. A total of 11 different disease causing mutations were found in four genes. Six of the mutations were previously not described. A novel mutation (a 33 base pair deletion) in the troponin I gene was found in one HCM family. Despite the severe genetic defect, the associated phenotype displayed only mild cardiac hypertrophy and few symptoms. Most mutations (64%) were identified in the myosin binding protein C gene, a gene considered to have a low penetrance. Mutations were identified in 10 of 11 familial HCM cases, but only in three of the 35 sporadic cases. It was found that cardiac amyloidosis can sometimes present itself as HCM. Three HCM patients (7%) carried the ATTR Val30Met mutation, also found in Swedish patients with familial amyloid polyneuropathy (FAP). The patients had no symptoms of polyneuropathy, but cardiac amyloidosis as the cause of hypertrophy was verified by myocardial biopsy in an index case. Amyloid heart disease should therefore be considered as a differential diagnosis in patients with HCM. By studying heart rate variability (HRV), it was found that young patients with HCM had signs of autonomic dysfunction, expressed as a reduced HRV. Treatment with beta-blockade attenuated these effects. Abnormal autonomic function might be a substrate for lethal arrhythmias, most often encountered in younger patients with HCM. The results suggest a possible protective effect of beta-blockade, remaining to be ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
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Umeå University: Publications (DiVA) |
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language |
English |
topic |
Hypertrophic cardiomyopathy genetics autonomic nervous system familial amyloid polyneuropathy echocardiography |
spellingShingle |
Hypertrophic cardiomyopathy genetics autonomic nervous system familial amyloid polyneuropathy echocardiography Mörner, Stellan Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
topic_facet |
Hypertrophic cardiomyopathy genetics autonomic nervous system familial amyloid polyneuropathy echocardiography |
description |
Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of this thesis was to identify the genotypes causing HCM in northern Sweden, to characterize the disease phenotypes and correlate these findings. Forty-six patients were recruited for the genetic studies (21 women), 11 familial and 35 sporadic cases. Eight sarcomeric protein genes were screened for mutations. A total of 11 different disease causing mutations were found in four genes. Six of the mutations were previously not described. A novel mutation (a 33 base pair deletion) in the troponin I gene was found in one HCM family. Despite the severe genetic defect, the associated phenotype displayed only mild cardiac hypertrophy and few symptoms. Most mutations (64%) were identified in the myosin binding protein C gene, a gene considered to have a low penetrance. Mutations were identified in 10 of 11 familial HCM cases, but only in three of the 35 sporadic cases. It was found that cardiac amyloidosis can sometimes present itself as HCM. Three HCM patients (7%) carried the ATTR Val30Met mutation, also found in Swedish patients with familial amyloid polyneuropathy (FAP). The patients had no symptoms of polyneuropathy, but cardiac amyloidosis as the cause of hypertrophy was verified by myocardial biopsy in an index case. Amyloid heart disease should therefore be considered as a differential diagnosis in patients with HCM. By studying heart rate variability (HRV), it was found that young patients with HCM had signs of autonomic dysfunction, expressed as a reduced HRV. Treatment with beta-blockade attenuated these effects. Abnormal autonomic function might be a substrate for lethal arrhythmias, most often encountered in younger patients with HCM. The results suggest a possible protective effect of beta-blockade, remaining to be ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Mörner, Stellan |
author_facet |
Mörner, Stellan |
author_sort |
Mörner, Stellan |
title |
Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
title_short |
Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
title_full |
Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
title_fullStr |
Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
title_full_unstemmed |
Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics |
title_sort |
hypertrophic cardiomyopathy in northern sweden : with special emphasis on molecular genetics |
publisher |
Institutionen för folkhälsa och klinisk medicin |
publishDate |
2004 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-274 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 894 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-274 urn:isbn:91-7305-660-X |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318112597835776 |