FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion.
Polyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led...
| Egile Nagusiak: | , , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
2014
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| _version_ | 1826285389975912448 |
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| author | Bäumer, D East, S Tseu, B Zeman, A Hilton, D Talbot, K Ansorge, O |
| author_facet | Bäumer, D East, S Tseu, B Zeman, A Hilton, D Talbot, K Ansorge, O |
| author_sort | Bäumer, D |
| collection | OXFORD |
| description | Polyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led to frontotemporal lobar degeneration with ALS (FTLD-ALS) in the index case, but typical SCA2 in a son, and compare the neuropathology with a case of typical SCA2. The index case shares the molecular signature of SCA2 with prominent polyglutamine and p62-positive intranuclear neuronal inclusions mainly in the pontine nuclei, while harbouring more pronounced neocortical and spinal TDP-43 pathology. We conclude that ATXN2 mutations can cause not only ALS, but also a neuropathological overlap syndrome of SCA2 and FTLD presenting clinically as pure FTLD-ALS without ataxia. The cause of the phenotypic heterogeneity remains unexplained, but the presence of a CAA-interrupted CAG repeat in the FTLD case in this family suggests that one potential mechanism may be variation in repeat tract composition between members of the same family. |
| first_indexed | 2024-03-07T01:28:06Z |
| format | Journal article |
| id | oxford-uuid:92a7ebb6-2315-4488-9935-1c6b13e51bfc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:28:06Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:92a7ebb6-2315-4488-9935-1c6b13e51bfc2022-03-26T23:27:05ZFTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:92a7ebb6-2315-4488-9935-1c6b13e51bfcEnglishSymplectic Elements at Oxford2014Bäumer, DEast, STseu, BZeman, AHilton, DTalbot, KAnsorge, OPolyglutamine expansions in the ataxin-2 gene (ATXN2) cause autosomal dominant spinocerebellar ataxia type 2 (SCA2), but have recently also been associated with amyotrophic lateral sclerosis (ALS). We present clinical and pathological features of a family in which a pathological ATXN2 expansion led to frontotemporal lobar degeneration with ALS (FTLD-ALS) in the index case, but typical SCA2 in a son, and compare the neuropathology with a case of typical SCA2. The index case shares the molecular signature of SCA2 with prominent polyglutamine and p62-positive intranuclear neuronal inclusions mainly in the pontine nuclei, while harbouring more pronounced neocortical and spinal TDP-43 pathology. We conclude that ATXN2 mutations can cause not only ALS, but also a neuropathological overlap syndrome of SCA2 and FTLD presenting clinically as pure FTLD-ALS without ataxia. The cause of the phenotypic heterogeneity remains unexplained, but the presence of a CAA-interrupted CAG repeat in the FTLD case in this family suggests that one potential mechanism may be variation in repeat tract composition between members of the same family. |
| spellingShingle | Bäumer, D East, S Tseu, B Zeman, A Hilton, D Talbot, K Ansorge, O FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title | FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title_full | FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title_fullStr | FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title_full_unstemmed | FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title_short | FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. |
| title_sort | ftld als of tdp 43 type and sca2 in a family with a full ataxin 2 polyglutamine expansion |
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