Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease
Background. Familial Amyloidosis with Polyneuropathy (FAP) is an autosomal dominantly inherited systemic amyloid disease. The disease is caused by mutations in the transthyretin (TTR) gene, where close to 100 different amyloidogenic mutations have been identified. FAP is found worldwide, but endemic...
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ftumeauniv:oai:DiVA.org:umu-34128 2023-10-09T21:54:39+02:00 Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease Familjär amyloidos med polyneuropati : studier av genetiska faktorer som modifierar sjukdomsfeneotypen Olsson, Malin 2010 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-34128 eng eng Medicin Medicinsk och klinisk genetik Umeå : Umeå university Umeå University medical dissertations, 0346-6612 1351 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-34128 urn:isbn:978-91-7459-005-0 info:eu-repo/semantics/openAccess Familial amyloid polyneuropathy Amyloidosis Transthyretin Allele Frequency Mitochondria parent-of-origin MicroRNA Single Nucleotide Polymorphism 3' Untranslated Regions/genetics Medical Genetics Medicinsk genetik Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2010 ftumeauniv 2023-09-22T13:49:43Z Background. Familial Amyloidosis with Polyneuropathy (FAP) is an autosomal dominantly inherited systemic amyloid disease. The disease is caused by mutations in the transthyretin (TTR) gene, where close to 100 different amyloidogenic mutations have been identified. FAP is found worldwide, but endemic areas with a high frequency of patients are found in Portugal, Japan and northern Sweden. Cases from these endemic areas all share the same TTR c.148G>A, p.V50M ("V30M") mutation, but the phenotype of the disease varies between the areas, and also within the endemic areas. The mean onset of the disease is two decades earlier in Portugal and Japan compared to Sweden, but late as well as early age at onset cases occur within all the populations. Interestingly, the different populations all display a maternal anticipation, where an earlier onset is observed for those individuals who inherit the trait from their mother. Since substantial variation in the phenotype is observed for different populations, epigenetic/genetic and/or environmental factors must exert a significant impact on the penetrance of the disease. Amyloid formation is caused by conformational changes of proteins, which facilitates their assembly into fibrils, amyloid. Oxidative stress can mediate conformational changes of proteins and since the mitochondria regulate oxidative processes within the cell, mitochondrial function may affect amyloid formation. The mitochondrial DNA is a non-nuclear DNA, which is entirely maternally inherited, and therefore could be related to the observed maternal anticipation of the disease. In addition, differences within the surrounding regions of the TTR gene may have an impact on the transcription of the gene and thereby on the expression of the different alleles. Material and methods. DNA from early and late onset V30M cases and from non-carriers (the latter utilised as controls) from Swedish, French, Japanese and Portuguese populations were analysed. In addition, DNA from healthy Swedish V30M carriers was analysed. ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Familial amyloid polyneuropathy Amyloidosis Transthyretin Allele Frequency Mitochondria parent-of-origin MicroRNA Single Nucleotide Polymorphism 3' Untranslated Regions/genetics Medical Genetics Medicinsk genetik |
spellingShingle |
Familial amyloid polyneuropathy Amyloidosis Transthyretin Allele Frequency Mitochondria parent-of-origin MicroRNA Single Nucleotide Polymorphism 3' Untranslated Regions/genetics Medical Genetics Medicinsk genetik Olsson, Malin Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
topic_facet |
Familial amyloid polyneuropathy Amyloidosis Transthyretin Allele Frequency Mitochondria parent-of-origin MicroRNA Single Nucleotide Polymorphism 3' Untranslated Regions/genetics Medical Genetics Medicinsk genetik |
description |
Background. Familial Amyloidosis with Polyneuropathy (FAP) is an autosomal dominantly inherited systemic amyloid disease. The disease is caused by mutations in the transthyretin (TTR) gene, where close to 100 different amyloidogenic mutations have been identified. FAP is found worldwide, but endemic areas with a high frequency of patients are found in Portugal, Japan and northern Sweden. Cases from these endemic areas all share the same TTR c.148G>A, p.V50M ("V30M") mutation, but the phenotype of the disease varies between the areas, and also within the endemic areas. The mean onset of the disease is two decades earlier in Portugal and Japan compared to Sweden, but late as well as early age at onset cases occur within all the populations. Interestingly, the different populations all display a maternal anticipation, where an earlier onset is observed for those individuals who inherit the trait from their mother. Since substantial variation in the phenotype is observed for different populations, epigenetic/genetic and/or environmental factors must exert a significant impact on the penetrance of the disease. Amyloid formation is caused by conformational changes of proteins, which facilitates their assembly into fibrils, amyloid. Oxidative stress can mediate conformational changes of proteins and since the mitochondria regulate oxidative processes within the cell, mitochondrial function may affect amyloid formation. The mitochondrial DNA is a non-nuclear DNA, which is entirely maternally inherited, and therefore could be related to the observed maternal anticipation of the disease. In addition, differences within the surrounding regions of the TTR gene may have an impact on the transcription of the gene and thereby on the expression of the different alleles. Material and methods. DNA from early and late onset V30M cases and from non-carriers (the latter utilised as controls) from Swedish, French, Japanese and Portuguese populations were analysed. In addition, DNA from healthy Swedish V30M carriers was analysed. ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Olsson, Malin |
author_facet |
Olsson, Malin |
author_sort |
Olsson, Malin |
title |
Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
title_short |
Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
title_full |
Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
title_fullStr |
Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
title_full_unstemmed |
Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
title_sort |
familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease |
publisher |
Medicin |
publishDate |
2010 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-34128 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 1351 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-34128 urn:isbn:978-91-7459-005-0 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318324532871168 |