Younkin, Steven G

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations.

Peter Kühnlein; Anne-Dorte Sperfeld; Ben Vanmassenhove; Vivianna Van Deerlin; Virginia M-Y Lee; John Q Trojanowski; Hans A Kretzschmar; Albert C Ludolph; Manuela Neumann (Profiled Authors: Lee, Virginia M-Y; Trojanowski, John Q)

Center for Neuropathology and Prion Research, Ludwig-Maximilians University, Munich, Feodor-Lynen-Strasse 23, 81377 Munich, Germany.
Archives of neurology 2008;65(9):1185-9.

BACKGROUND: Abnormal neuronal inclusions composed of the transactivation response DNA-binding protein 43 (TDP-43) are characteristic neuropathologic lesions in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). This makes TARDBP, the gene encoding for TDP-43, a candidate for genetic screening in ALS. OBJECTIVES: To investigate the presence and frequency of TARDBP mutations in ALS. DESIGN: Genetic analysis. SETTING: Academic research. PARTICIPANTS: One hundred thirty-four patients with sporadic ALS, 31 patients with familial non-superoxide dismutase 1 gene (non-SOD1) (OMIM 147450) ALS, and 400 healthy control subjects. MAIN OUTCOME MEASURES: We identified 2 missense mutations (G348C and the novel N352S) in TARDBP in 2 small kindreds with a hereditary form of ALS with early spinal onset resulting in fatal respiratory insufficiency without clinical relevant bulbar symptoms or signs of cognitive impairment. RESULTS: The mutations located in the C-terminus of TDP-43 were absent in 400 controls of white race/ethnicity. The novel identified N352S mutation is predicted to increase TDP-43 phosphorylation, while the G348C mutation might interfere with normal TDP-43 function by forming intermolecular disulfide bridges. CONCLUSIONS: Mutations in TARDBP are a rare cause of familial non-SOD1 ALS. The identification of TARDBP mutations provides strong evidence for a direct link between TDP-43 dysfunction and neurodegeneration in ALS.

2 Originating Grant

• 1.

  LEE, VIRGINIA M

  Frontotemporal Dementias: Genotypes and Phenotypes

  15 March 2000 - 29 February 2016

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 21,445,858

• 2.

  TROJANOWSKI, JOHN Q.

  Alzheimer's Disease Core Center

  15 July 1997 - 30 June 2016

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 25,158,594

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.