Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May;11(2):217-25.
doi: 10.1007/s10048-009-0218-9. Epub 2009 Sep 17.

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

Janine Kirby  1 , Emily F Goodall, William Smith, J Robin Highley, Rudo Masanzu, Judith A Hartley, Rachel Hibberd, Hannah C Hollinger, Stephen B Wharton, Karen E Morrison, Paul G Ince, Christopher J McDermott, Pamela J Shaw
Affiliations
Free article

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

Janine Kirby et al. Neurogenetics. 2010 May.
Free article

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. PLoS One. 2008 Jun 11;3(6):e2450 - PubMed
    1. EMBO J. 2001 Apr 2;20(7):1774-84 - PubMed
    1. J Neurol Sci. 2000 Nov 1;180(1-2):15-20 - PubMed
    1. Arch Neurol. 2008 Sep;65(9):1185-9 - PubMed
    1. J Med Genet. 2009 Feb;46(2):112-4 - PubMed

Publication types

Substances

LinkOut - more resources