Journal ArticleDOI
Exploring the correlates of intermediate CAG repeats in Huntington disease.
Ainhi D. Ha,Joseph Jankovic +1 more
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TLDR
Individuals with huntingtin gene CAG repeats in the intermediate (27-35) range should be considered at risk for the development ofHD, particularly if they have a family history of HD, whether they exhibit clinical features of the disease.Abstract:
Objective: To explore the clinical phenotype in individuals with huntingtin gene CAG repeat lengths between 27 and 35, a range that is termed “intermediate” and below one traditionally considered diagnostic of Huntington disease (HD). Background: The Prospective Huntington Disease At-Risk Observational Study (PHAROS) found that patients with intermediate CAG lengths overlapped with those diagnosed as HD (≤ 37 CAG repeats) on the Unified Huntington's Disease Rating Scale (UHDRS) behavioral measures. Furthermore, several patients with intermediate CAG repeats demonstrating clinical (and pathological) evidence of HD have been reported. Methods: We reviewed all cases with intermediate CAG repeats who have presented to our clinic, as well as those reported in the literature. Results: We describe 4 patients with intermediate repeats evaluated at our center whose clinical features were highly suggestive of HD. Investigations for HD phenocopies were negative. Anticipation was demonstrated in 1 case with s...read more
Citations
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Journal ArticleDOI
Dopamine: Functions, Signaling, and Association with Neurological Diseases
Marianne O. Klein,Daniella S. Battagello,Ariel R. Cardoso,David N. Hauser,Jackson C. Bittencourt,Ricardo G. Correa +5 more
TL;DR: The aspects of dopamine as a catecholaminergic neurotransmitter and dopamine signaling pathways elicited through dopamine receptor activation in normal brain function are summarized and the potential involvement of these signaling pathways in evoking the onset and progression of some diseases in the nervous system are described.
Journal ArticleDOI
Huntington disease: pathogenesis and treatment.
Praveen Dayalu,Roger L. Albin +1 more
TL;DR: The current knowledge of HD pathogenesis and treatment is reviewed, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments.
Journal ArticleDOI
Huntington's disease.
Ainhi D Ha,Victor S.C. Fung +1 more
TL;DR: The prodromal stage of Huntington's disease provides an ideal period for the use of disease-modifying therapy and a quantifiable and reliable biomarker for monitoring disease progression is crucial for clinical studies of neuroprotection, and this remains an area of active research.
Journal ArticleDOI
Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS
Annie Killoran,Kevin M. Biglan,Joseph Jankovic,Shirley Eberly,Elise Kayson,David Oakes,Anne B. Young,Ira Shoulson +7 more
TL;DR: In a cohort at risk for HD, the IA was associated with significant behavioral abnormalities but normal motor and cognition, and may represent a prodromal stage of HD, with the potential for subsequent clinical manifestations.
Journal ArticleDOI
Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation
TL;DR: The mechanism of interaction between a huntingtin exon 1 fragment of increasing polyQ lengths (HttEx1Qn), the aggregation of which is tightly associated with Huntington's disease, and molecular chaperone Hsc70 is dissected to lay the foundations of future therapeutic strategies targeting huntingtin aggregation in Huntington disease.
References
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Journal ArticleDOI
Huntington's disease.
TL;DR: Effective intervention by clinicians is possible in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.
Journal ArticleDOI
Huntington's disease New approaches to an old problem: The Robert Wartenberg Lecture
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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
Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset
Nancy S. Wexler,Judith Lorimer,Julie Porter,Fidela Gomez,Carol Moskowitz,Edith Shackell,Karen Marder,Penchaszadeh Gk,Simone A. Roberts,Javier Gayán,Denise Brocklebank,Stacey S. Cherny,Lon R. Cardon,Jacqueline Gray,Stephen R. Dlouhy,Sandra Wiktorski,Marion E. Hodes,P. Michael Conneally,J. B. Penney,James F. Gusella,Jang Ho Cha,Michael C. Irizarry,Diana Rosas,Steven M. Hersch,Zane R. Hollingsworth,Marcy E. MacDonald,Anne B. Young,J. Michael Andresen,David E. Housman,Margot de Young,Ernesto Bonilla,Theresa Stillings,Américo Negrette,S. Robert Snodgrass,Maria Dolores Martinez-Jaurrieta,Maria A. Ramos-Arroyo,Jacqueline Bickham,Juan Sanchez Ramos,Frederick J. Marshall,Ira Shoulson,Gustavo Rey,Andrew Feigin,Norman Arnheim,Amarilis Acevedo-Cruz,Leticia Acosta,Jose Alvir,Kenneth H. Fischbeck,Leslie M. Thompson,Angela Young,Leon S. Dure,Christopher J. O'Brien,Jane S. Paulsen,Adam M. Brickman,Denise Krch,Shelley Peery,Penelope Hogarth,Donald S. Higgins,Bernhard Landwehrmeyeri +57 more
TL;DR: A model estimated the components of additive genetic, shared environment, and nonshared environment variances confirming that approximately 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental.
Journal ArticleDOI
OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells
TL;DR: It is shown that the age-dependent somatic mutation associated with Huntington’s disease occurs in the process of removing oxidized base lesions, and is remarkably dependent on a single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1).
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