Journal ArticleDOI
A Comprehensive Review of Spinocerebellar Ataxia Type 2 in Cuba
Luis Velázquez-Pérez,Roberto Rodríguez-Labrada,Julio Cesar García-Rodríguez,Luis E. Almaguer-Mederos,Tania Cruz-Mariño,José Miguel Laffita-Mesa +5 more
TLDR
The comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and pre-symptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities are highlighted.Abstract:
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia characterized by a progressive cerebellar syndrome associated to saccadic slowing, peripheral neuropathy, cognitive disorders, and other multisystem features. SCA2 is caused by the abnormal expansion of cytosine–adenine–guanine triplet repeats in the encoding region of the ATXN2 gene and therefore the expression of toxic polyglutamine expansions in the ataxin 2 protein, which cause progressive neuronal death of Purkinje cells in the cerebellum and several pontine, mesencephalic, and thalamic neurons among other cells. Worldwide, SCA2 is the second most frequent type of spinocerebellar ataxia, only surpassed by SCA3. Nevertheless, in Holguin, Cuba, the disease reaches the highest prevalence, resulting from a putative foundational effect. This review discusses the most important advances in the genotypical and phenotypical studies of SCA2, highlighting the comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and pre-symptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities. These findings provide guidelines, from a Cuban viewpoint, for the clinical management of the disease, its diagnosis, genetic counseling, and therapeutical options through rehabilitative therapy and/or pharmacological options.read more
Citations
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Book ChapterDOI
Spinocerebellar Ataxia Type 2
TL;DR: The autosomal dominant cerebellar ataxias are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections.
Journal ArticleDOI
Spinocerebellar ataxia type 2: clinical presentation, molecular mechanisms, and therapeutic perspectives.
TL;DR: Based on previous experience with other polyglutamine disorders and considering the molecular basis of SCA2 pathogenesis, a nuclei-acid-based strategy focused on the specific silencing of the dominant disease allele that preserves the expression of the wild-type allele is highly desirable and might prevent toxic neurodegenerative sequelae.
Journal ArticleDOI
Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study
Luis Velázquez-Pérez,Roberto Rodríguez-Labrada,Nalia Canales-Ochoa,Jacqueline Medrano Montero,Sánchez-Cruz G,Raúl Aguilera-Rodríguez,Luis E. Almaguer-Mederos,José Miguel Laffita-Mesa +7 more
TL;DR: Early features of SCA2 are detectable before the onset of the cerebellar syndrome, and are associated with expanded CAG repeats and the time to onset of cerebellary syndrome.
Journal ArticleDOI
Spinocerebellar Ataxia Type 2: Clinicogenetic Aspects, Mechanistic Insights, and Management Approaches
TL;DR: Neuropathological investigations of brain tissue from SCA2 patients reveal a widespread involvement of multiple brain systems, mainly cerebellar and brainstem systems, and insights into the ataxin-2-related toxicity mechanism in neurodegenerative diseases are provided.
Journal ArticleDOI
Comprehensive Study of Early Features in Spinocerebellar Ataxia 2: Delineating the Prodromal Stage of the Disease
Luis Velázquez-Pérez,Roberto Rodríguez-Labrada,Edilia M. Cruz-Rivas,Juan Fernandez-Ruiz,Israel Vaca-Palomares,Jandy Lilia-Campins,Bulmaro Cisneros,Arnoy Peña-Acosta,Yaimeé Vázquez-Mojena,Rosalinda Diaz,Jonathan J. Magaña-Aguirre,Tania Cruz-Mariño,Annelié Estupiñán-Rodríguez,José Miguel Laffita-Mesa,Rigoberto González-Piña,Nalia Canales-Ochoa,Yanetza González-Zaldivar +16 more
TL;DR: The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.
References
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Journal ArticleDOI
Scale for the assessment and rating of ataxia: development of a new clinical scale.
T. Schmitz-Hübsch,S. Tezenas du Montcel,Laszlo Baliko,José Berciano,S Boesch,Chantal Depondt,Paola Giunti,C. Globas,Jon Infante,J-S Kang,Berry Kremer,Christian Mariotti,Béla Melegh,Massimo Pandolfo,Maryla Rakowicz,P Ribai,Rafał Rola,Ludger Schöls,Sandra Szymanski,B.P.C. van de Warrenburg,Alexandra Durr,Thomas Klockgether,Roberto Fancellu +22 more
TL;DR: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.
Journal ArticleDOI
Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS
Andrew Elden,Hyung-Jun Kim,Michael P. Hart,Alice Chen-Plotkin,Brian S. Johnson,Xiaodong Fang,Maria Armakola,Felix Geser,Robert W. Greene,Min Min Lu,Arun Padmanabhan,Dana Clay-Falcone,Leo McCluskey,Lauren Elman,Denise Juhr,Peter J. Gruber,Udo Rüb,Georg Auburger,John Q. Trojanowski,Virginia M.-Y. Lee,Vivianna M. Van Deerlin,Nancy M. Bonini,Aaron D. Gitler +22 more
TL;DR: It is shown that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models.
Journal ArticleDOI
Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2
Stefan M. Pulst,Alex Nechiporuk,Alex Nechiporuk,Tamilla Nechiporuk,Tamilla Nechiporuk,Suzana Gispert,Xiao Ning Chen,Iscia Lopes-Cendes,Susan Pearlman,Sidney Starkman,Guillermo Orozco-Diaz,Astrid Lunkes,Pieter DeJong,Guy A. Rouleau,Georg Auburger,Julie R. Korenberg,Carla P. Figueroa,Carla P. Figueroa,Soodabeh Sahba,Soodabeh Sahba +19 more
TL;DR: A CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2, which is a member of a novel gene family and not highly polymorphic in normal individuals is identified.
Journal ArticleDOI
Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis.
TL;DR: The identification of ataxia genes raises hope that essential pathogenetic mechanisms causing SCA will become more and more apparent, and will enable the development of rational therapies for this group of disorders, which currently can only be treated symptomatically.
Journal ArticleDOI
Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats
Georges Imbert,Frédéric Saudou,Frédéric Saudou,Gaël Yvert,Gaël Yvert,Didier Devys,Didier Devys,Yvon Trottier,Yvon Trottier,Jean-Marie Garnier,Jean-Marie Garnier,Chantal Weber,Chantal Weber,Jean-Louis Mandel,Jean-Louis Mandel,Géraldine Cancel,Géraldine Cancel,Nacer Abbas,Nacer Abbas,Alexandra Durr,Alexandra Durr,Olivier Didierjean,Olivier Didierjean,Giovanni Stevanin,Giovanni Stevanin,Yves Agid,Yves Agid,Alexis Brice,Alexis Brice +28 more
TL;DR: The steep inverse correlation between age of onset and CAG number suggests a higher sensitivity to polyglutamine length than in the other polyglUTamine expansion diseases.
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Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2
Stefan M. Pulst,Alex Nechiporuk,Alex Nechiporuk,Tamilla Nechiporuk,Tamilla Nechiporuk,Suzana Gispert,Xiao Ning Chen,Iscia Lopes-Cendes,Susan Pearlman,Sidney Starkman,Guillermo Orozco-Diaz,Astrid Lunkes,Pieter DeJong,Guy A. Rouleau,Georg Auburger,Julie R. Korenberg,Carla P. Figueroa,Carla P. Figueroa,Soodabeh Sahba,Soodabeh Sahba +19 more
Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin.
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Scale for the assessment and rating of ataxia: development of a new clinical scale.
T. Schmitz-Hübsch,S. Tezenas du Montcel,Laszlo Baliko,José Berciano,S Boesch,Chantal Depondt,Paola Giunti,C. Globas,Jon Infante,J-S Kang,Berry Kremer,Christian Mariotti,Béla Melegh,Massimo Pandolfo,Maryla Rakowicz,P Ribai,Rafał Rola,Ludger Schöls,Sandra Szymanski,B.P.C. van de Warrenburg,Alexandra Durr,Thomas Klockgether,Roberto Fancellu +22 more
Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats
Georges Imbert,Frédéric Saudou,Frédéric Saudou,Gaël Yvert,Gaël Yvert,Didier Devys,Didier Devys,Yvon Trottier,Yvon Trottier,Jean-Marie Garnier,Jean-Marie Garnier,Chantal Weber,Chantal Weber,Jean-Louis Mandel,Jean-Louis Mandel,Géraldine Cancel,Géraldine Cancel,Nacer Abbas,Nacer Abbas,Alexandra Durr,Alexandra Durr,Olivier Didierjean,Olivier Didierjean,Giovanni Stevanin,Giovanni Stevanin,Yves Agid,Yves Agid,Alexis Brice,Alexis Brice +28 more