Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis
Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis
The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction.
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Kirby, Janine
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Goodall, Emily F.
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Smith, William
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Highley, J. Robin
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Masanzu, Rudo
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Hartley, Judith A.
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Hibberd, Rachel
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Hollinger, Hannah C.
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Wharton, Stephen B.
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Morrison, Karen E.
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Ince, Paul G.
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McDermott, Christopher J.
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Shaw, Pamela J.
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May 2010
Kirby, Janine
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Goodall, Emily F.
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Smith, William
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Highley, J. Robin
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Masanzu, Rudo
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Hartley, Judith A.
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Hibberd, Rachel
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Hollinger, Hannah C.
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Wharton, Stephen B.
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Morrison, Karen E.
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Ince, Paul G.
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McDermott, Christopher J.
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Shaw, Pamela J.
3d0a5c6f-9610-45be-a0bc-5b6888003028
Kirby, Janine, Goodall, Emily F., Smith, William, Highley, J. Robin, Masanzu, Rudo, Hartley, Judith A., Hibberd, Rachel, Hollinger, Hannah C., Wharton, Stephen B., Morrison, Karen E., Ince, Paul G., McDermott, Christopher J. and Shaw, Pamela J.
(2010)
Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis.
Neurogenetics, 11 (2), .
(doi:10.1007/s10048-009-0218-9).
Abstract
The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction.
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Accepted/In Press date: 20 August 2009
Published date: May 2010
Organisations:
Medical Education
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Local EPrints ID: 398769
URI: http://eprints.soton.ac.uk/id/eprint/398769
ISSN: 1364-6745
PURE UUID: 7302cc3e-029f-4d20-b363-3a943c19ab2f
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Date deposited: 01 Aug 2016 14:10
Last modified: 15 Mar 2024 01:42
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Contributors
Author:
Janine Kirby
Author:
Emily F. Goodall
Author:
William Smith
Author:
J. Robin Highley
Author:
Rudo Masanzu
Author:
Judith A. Hartley
Author:
Rachel Hibberd
Author:
Hannah C. Hollinger
Author:
Stephen B. Wharton
Author:
Karen E. Morrison
Author:
Paul G. Ince
Author:
Christopher J. McDermott
Author:
Pamela J. Shaw
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