Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA
Abstract Neurological features are common in mitochondrial diseases because tissues depending upon oxidative phosphorylation bear the brunt of the pathogenesis. The 3243A>G mutation in the MTTL1 gene in mitochondrial DNA is regarded as the most frequent mitchondrial point mutation and classically...
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University of Oulu
2004
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ftunivoulu:oai:oulu.fi:isbn951-42-7364-8 2023-07-30T04:05:50+02:00 Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA Kärppä, M. (Mikko) 2004-03-19 application/pdf http://urn.fi/urn:isbn:9514273648 eng eng University of Oulu info:eu-repo/semantics/altIdentifier/pissn/0355-3221 info:eu-repo/semantics/altIdentifier/eissn/1796-2234 info:eu-repo/semantics/openAccess © University of Oulu, 2004 3243A>G mutation MELAS heteroplasmy mitochondrial DNA myopathy peripheral neuropathy phenotype info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion 2004 ftunivoulu 2023-07-08T20:01:20Z Abstract Neurological features are common in mitochondrial diseases because tissues depending upon oxidative phosphorylation bear the brunt of the pathogenesis. The 3243A>G mutation in the MTTL1 gene in mitochondrial DNA is regarded as the most frequent mitchondrial point mutation and classically presents with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Myopathy and peripheral neuropathy have been documented in patients with mitochondrial diseases, but not properly characterised in patients with the 3243A>G mutation. We have previously determined the prevalence of patients with this mutation in a defined population in northern Finland. The clinical spectrum and molecular aspects of myopathy and peripheral neuropathy are analysed here in a population-based cohort of patients with 3243A>G. Fifty patients were examined neurologically in order to define the frequency of myopathy and its histological, ultrastructural and clinical features. The frequency and phenotypic variability of peripheral neuropathy were determined in 32 patients and muscle computed tomography findings recorded in 24 patients. Finally, variations in mutation heteroplasmy were analysed in 10 patients using single muscle fibre PCR analysis. The frequency of peripheral neuropathy was 22% (95% confidence interval (CI), 9–40%) and that of clinical myopathy 50% (95% CI, 36–64%). Moderate limb weakness was the most common myopathic feature, but mild weakness and external ophthalmoplegia were also present. CT scans revealed myopathic changes in 54% of the patients (95% CI, 33–76%), most frequently in the pelvic muscles. The incidence of myopathy was highest in the fifth decade of life, and higher age and male gender increased the risk of neuropathy. Muscle histology was abnormal in 72% of the cases examined (95% CI, 55–86%). The presence of intramitochondrial crystals and COX-negative fibres and variations in the size and shape of mitochondria were more common in the muscle of myopathic patients. Single ... Doctoral or Postdoctoral Thesis Northern Finland Jultika - University of Oulu repository |
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Jultika - University of Oulu repository |
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ftunivoulu |
language |
English |
topic |
3243A>G mutation MELAS heteroplasmy mitochondrial DNA myopathy peripheral neuropathy phenotype |
spellingShingle |
3243A>G mutation MELAS heteroplasmy mitochondrial DNA myopathy peripheral neuropathy phenotype Kärppä, M. (Mikko) Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
topic_facet |
3243A>G mutation MELAS heteroplasmy mitochondrial DNA myopathy peripheral neuropathy phenotype |
description |
Abstract Neurological features are common in mitochondrial diseases because tissues depending upon oxidative phosphorylation bear the brunt of the pathogenesis. The 3243A>G mutation in the MTTL1 gene in mitochondrial DNA is regarded as the most frequent mitchondrial point mutation and classically presents with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Myopathy and peripheral neuropathy have been documented in patients with mitochondrial diseases, but not properly characterised in patients with the 3243A>G mutation. We have previously determined the prevalence of patients with this mutation in a defined population in northern Finland. The clinical spectrum and molecular aspects of myopathy and peripheral neuropathy are analysed here in a population-based cohort of patients with 3243A>G. Fifty patients were examined neurologically in order to define the frequency of myopathy and its histological, ultrastructural and clinical features. The frequency and phenotypic variability of peripheral neuropathy were determined in 32 patients and muscle computed tomography findings recorded in 24 patients. Finally, variations in mutation heteroplasmy were analysed in 10 patients using single muscle fibre PCR analysis. The frequency of peripheral neuropathy was 22% (95% confidence interval (CI), 9–40%) and that of clinical myopathy 50% (95% CI, 36–64%). Moderate limb weakness was the most common myopathic feature, but mild weakness and external ophthalmoplegia were also present. CT scans revealed myopathic changes in 54% of the patients (95% CI, 33–76%), most frequently in the pelvic muscles. The incidence of myopathy was highest in the fifth decade of life, and higher age and male gender increased the risk of neuropathy. Muscle histology was abnormal in 72% of the cases examined (95% CI, 55–86%). The presence of intramitochondrial crystals and COX-negative fibres and variations in the size and shape of mitochondria were more common in the muscle of myopathic patients. Single ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Kärppä, M. (Mikko) |
author_facet |
Kärppä, M. (Mikko) |
author_sort |
Kärppä, M. (Mikko) |
title |
Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
title_short |
Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
title_full |
Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
title_fullStr |
Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
title_full_unstemmed |
Myopathy and peripheral neuropathy associated with the 3243A>G mutation in mitochondrial DNA |
title_sort |
myopathy and peripheral neuropathy associated with the 3243a>g mutation in mitochondrial dna |
publisher |
University of Oulu |
publishDate |
2004 |
url |
http://urn.fi/urn:isbn:9514273648 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
info:eu-repo/semantics/altIdentifier/pissn/0355-3221 info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
op_rights |
info:eu-repo/semantics/openAccess © University of Oulu, 2004 |
_version_ |
1772818082161491968 |