Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease
<p>Abstract</p> <p>Background</p> <p>Many cases of frontotemporal dementia (FTD) are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in br...
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| Format: | Article |
| Language: | English |
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BMC
2006-08-01
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| Series: | BMC Neurology |
| Online Access: | http://www.biomedcentral.com/1471-2377/6/32 |
| _version_ | 1819027921874976768 |
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| author | Neal Scott J Lindholm Caroline Feldman Howard Dwosh Emily Devon Rebecca S Butland Stefanie L Mackenzie Ian R Ouellette BF Francis Leavitt Blair R |
| author_facet | Neal Scott J Lindholm Caroline Feldman Howard Dwosh Emily Devon Rebecca S Butland Stefanie L Mackenzie Ian R Ouellette BF Francis Leavitt Blair R |
| author_sort | Neal Scott J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Many cases of frontotemporal dementia (FTD) are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in brain tissue (FTDP-17T). Most of the remaining familial cases do not exhibit tau pathology, but display neuropathology similar to patients with dementia and motor neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub-ir), dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and hippocampus (FTLD-U). Recently, we described a subset of patients with familial FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir neuronal intranuclear inclusions (NII). NII are a characteristic feature of several other neurodegenerative conditions for which the genetic basis is abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease.</p> <p>Methods</p> <p>We studied DNA and post mortem brain tissue from 5 affected members of 4 different families with NII and one affected individual with familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide expansion in a set of candidate genes identified using a genome-wide computational approach. Genes containing CAA/CAG trinucleotide repeats encoding at least five glutamines were examined (n = 63), including the nine genes currently known to be associated with human disease. CAA/CAG tract sizes were compared with published normal values (where available) and with those of healthy controls (n = 94). High-resolution agarose gel electrophoresis was used to measure allele size (number of CAA/CAG repeats). For any alleles estimated to be equal to or larger than the maximum measured in the control population, the CAA/CAG tract length was confirmed by capillary electrophoresis. In addition, immunohistochemistry using a monoclonal antibody that recognizes proteins containing expanded polyglutamines (1C2) was performed on sections of post mortem brain tissue from subjects with NII.</p> <p>Results</p> <p>No significant polyglutamine-encoding repeat expansions were identified in the DNA from any of our FTLD-U patients. NII in the FTLD-U cases showed no 1C2 immunoreactivity.</p> <p>Conclusion</p> <p>We find no evidence to suggest that autosomal dominant FTLD-U with NII is a polyglutamine expansion disease.</p> |
| first_indexed | 2024-12-21T05:50:09Z |
| format | Article |
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| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-21T05:50:09Z |
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| spelling | doaj.art-055cc9922424449790938a12de08ef672022-12-21T19:14:00ZengBMCBMC Neurology1471-23772006-08-01613210.1186/1471-2377-6-32Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion diseaseNeal Scott JLindholm CarolineFeldman HowardDwosh EmilyDevon Rebecca SButland Stefanie LMackenzie Ian ROuellette BF FrancisLeavitt Blair R<p>Abstract</p> <p>Background</p> <p>Many cases of frontotemporal dementia (FTD) are familial, often with an autosomal dominant pattern of inheritance. Some are due to a mutation in the tau- encoding gene, on chromosome 17, and show an accumulation of abnormal tau in brain tissue (FTDP-17T). Most of the remaining familial cases do not exhibit tau pathology, but display neuropathology similar to patients with dementia and motor neuron disease, characterized by the presence of ubiquitin-immunoreactive (ub-ir), dystrophic neurites and neuronal cytoplasmic inclusions in the neocortex and hippocampus (FTLD-U). Recently, we described a subset of patients with familial FTD with autopsy-proven FTLD-U pathology and with the additional finding of ub-ir neuronal intranuclear inclusions (NII). NII are a characteristic feature of several other neurodegenerative conditions for which the genetic basis is abnormal expansion of a polyglutamine-encoding trinucleotide repeat region. The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease.</p> <p>Methods</p> <p>We studied DNA and post mortem brain tissue from 5 affected members of 4 different families with NII and one affected individual with familial FTLD-U without NII. Patient DNA was screened for CAA/CAG trinucleotide expansion in a set of candidate genes identified using a genome-wide computational approach. Genes containing CAA/CAG trinucleotide repeats encoding at least five glutamines were examined (n = 63), including the nine genes currently known to be associated with human disease. CAA/CAG tract sizes were compared with published normal values (where available) and with those of healthy controls (n = 94). High-resolution agarose gel electrophoresis was used to measure allele size (number of CAA/CAG repeats). For any alleles estimated to be equal to or larger than the maximum measured in the control population, the CAA/CAG tract length was confirmed by capillary electrophoresis. In addition, immunohistochemistry using a monoclonal antibody that recognizes proteins containing expanded polyglutamines (1C2) was performed on sections of post mortem brain tissue from subjects with NII.</p> <p>Results</p> <p>No significant polyglutamine-encoding repeat expansions were identified in the DNA from any of our FTLD-U patients. NII in the FTLD-U cases showed no 1C2 immunoreactivity.</p> <p>Conclusion</p> <p>We find no evidence to suggest that autosomal dominant FTLD-U with NII is a polyglutamine expansion disease.</p>http://www.biomedcentral.com/1471-2377/6/32 |
| spellingShingle | Neal Scott J Lindholm Caroline Feldman Howard Dwosh Emily Devon Rebecca S Butland Stefanie L Mackenzie Ian R Ouellette BF Francis Leavitt Blair R Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease BMC Neurology |
| title | Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| title_full | Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| title_fullStr | Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| title_full_unstemmed | Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| title_short | Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| title_sort | familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease |
| url | http://www.biomedcentral.com/1471-2377/6/32 |
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