Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias

Human Molecular Genetics
G StevaninA Brice

Abstract

Expansion of trinucleotide CAG repeats coding for polyglutamine has been implicated in five neurodegenerative disorders, including spinocerebellar ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which specifically recognizes large polyglutamine tracts, particularly those that are expanded, we recently reported the detection of proteins with pathological glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as well as from patients presenting with the distinct phenotype of ADCA type II. We now have screened a large series of patients with ADCA or isolated cases with cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This corresponds to 24% of all ADCA type I families, which is much more frequent than SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein was negatively correlated to age at onset, as expected for an expanded and unstable trinucleotide repeat mutation. The disease segregated with markers closely linked to the SCA2 locus in all identified SCA2 families. In addit...Continue Reading

Citations

Jul 7, 2005·Journal of Neurology·Y HellenbroichCh Zühlke
Apr 18, 2008·The Cerebellum·Giovanni Stevanin, Alexis Brice
Dec 12, 2001·Neurochemistry International·Soo Youl KimPeter M Steinert
Jun 14, 2000·Clinical Genetics·G ClarkeR R McInnes
Sep 25, 1997·Human Molecular Genetics·J E NielsenS A Sørensen
Sep 16, 1998·Human Molecular Genetics·G StevaninA Brice
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A LunkesJ L Mandel
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A S HackamM R Hayden
Sep 1, 2005·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A InagakiH Inagaki
Jun 9, 2000·Annual Review of Neuroscience·H Y Zoghbi, H T Orr
Jan 6, 2004·Annals of Neurology·Giovanni StevaninAlexis Brice
Jun 12, 2008·Movement Disorders : Official Journal of the Movement Disorder Society·Juan ForteaTeresa Ribalta
Jul 22, 2008·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·E Storey
May 17, 2000·American Journal of Medical Genetics·J B VincentJ L Kennedy
Oct 23, 2003·European Journal of Human Genetics : EJHG·A MichalikC Van Broeckhoven
Oct 27, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michel CyrMarc G Caron
Aug 23, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anna Niewiadomska-Cimicka, Yvon Trottier
May 24, 2003·Brain : a Journal of Neurology·Ming-Yi ChungBing-Wen Soong
Mar 29, 2000·Journal of Neurochemistry·W J GuA Brice
Nov 23, 2020·Neuroscience Letters·Shujun JiaoHong Jiang
May 8, 2021·Clinical Genetics·Lucas Schenatto SenaLaura Bannach Jardim

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