Access the full text.
Sign up today, get DeepDyve free for 14 days.
K. Gwinn‐Hardy, J. Chen, H. Liu, T. Liu, M. Boss, W. Seltzer, A. Adam, A. Singleton, W. Koroshetz, C. Waters, J. Hardy, M. Farrer (2000)
Spinocerebellar ataxia type 2 with parkinsonism in ethnic ChineseNeurology, 55
M. Socal, V. Emmel, C. Rieder, A. Hilbig, M. Saraiva-Pereira, L. Jardim (2009)
Intrafamilial variability of Parkinson phenotype in SCAs: novel cases due to SCA2 and SCA3 expansions.Parkinsonism & related disorders, 15 5
B. Dehay, A. Bertolotti (2006)
Critical Role of the Proline-rich Region in Huntingtin for Aggregation and Cytotoxicity in Yeast*Journal of Biological Chemistry, 281
Furtado (2002)
SCA-2 presenting as parkinsonism in an Alberta family: Clinical, genetic, and PET findingsNeurology, 59
K. Sobczak, W. Krzyzosiak (2005)
CAG Repeats Containing CAA Interruptions Form Branched Hairpin Structures in Spinocerebellar Ataxia Type 2 Transcripts*Journal of Biological Chemistry, 280
G. Imbert, F. Saudou, G. Yvert, D. Devys, Y. Trottier, J. Garnier, C. Weber, J. Mandel, G. Cancel, N. Abbas, A. Dürr, O. Didierjean, G. Stevanin, Y. Agid, A. Brice (1996)
Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeatsNature Genetics, 14
C. Lu, Y. Chou, T. Yen, C. Tsai, Rou-shayn Chen, Hsiu-Chen Chang (2002)
Dopa‐responsive parkinsonism phenotype of spinocerebellar ataxia type 2Movement Disorders, 17
J. Pang, R. Allotey, N. Wadia, H. Sasaki, L. Bindoff, S. Chamberlain (1999)
A common disease haplotype segregating in spinocerebellar ataxia 2 (SCA2) pedigrees of diverse ethnic originEuropean Journal of Human Genetics, 7
(2000)
An interrupted 34-CAG repeat SCA-2 allele in patients with sporadic spinocerebellar ataxia
Jong-Min Kim, Susie Hong, Gyoung Kim, Y. Choi, Yu Kim, S. Park, Sang Kim, B. Jeon (2007)
Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism.Archives of neurology, 64 10
J. Hardy (2002)
Faculty Opinions recommendation of SCA-2 presenting as parkinsonism in an Alberta family: clinical, genetic, and PET findings.
K. Sanpei, H. Takano, S. Igarashi, Toshiya Sato, M. Oyake, H. Sasaki, A. Wakisaka, K. Tashiro, Y. Ishida, T. Ikeuchi, R. Koide, M. Saito, A. Sato, Toshihisa Tanaka, S. Hanyu, Y. Takiyama, M. Nishizawa, N. Shimizu, Y. Nomura, M. Segawa, K. Iwabuchi, I. Eguchi, Hirosato Tanaka, H. Takahashi, S. Tsuji (1996)
Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECTNature Genetics, 14
Ataxic disorders. Handbook of neurological disorders
A. Brusco, C. Gellera, C. Cagnoli, A. Saluto, Alessia Castucci, C. Michielotto, V. Fetoni, C. Mariotti, N. Migone, S. Donato, F. Taroni (2004)
Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families.Archives of neurology, 61 5
L. Velázquez-Pérez, Santos Fn, R. García, Paneque Hm, Hechavarría Pr (2001)
[Epidemiology of Cuban hereditary ataxia].Revista de neurologia, 32 7
M. Fernandez, M. McClain, R. Martinez, K. Snow, H. Lipe, J. Ravits, T. Bird, A. Spada (2000)
Late-onset SCA2: 33 CAG repeats are sufficient to cause diseaseNeurology, 55
S. Choudhry, M. Mukerji, A. Srivastava, Satish Jain, S. Brahmachari (2001)
CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.Human molecular genetics, 10 21
N. Wadia, J. Pang, J. Desai, A. Mankodi, Margi Desai, S. Chamberlain (1998)
A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis.Brain : a journal of neurology, 121 ( Pt 12)
A. Khoshnan, J. Ko, P. Patterson (2002)
Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicityProceedings of the National Academy of Sciences of the United States of America, 99
N. Suite, J. Sequeiros, G. Mckhann (1986)
Machado-Joseph disease in a Sicilian-American family.Journal of neurogenetics, 3 3
J. Sequeiros, Sandra Martins, I. Silveira (2012)
Epidemiology and population genetics of degenerative ataxias.Handbook of clinical neurology, 103
I. Silveira, C. Miranda, L. Guimarães, M. Moreira, I. Alonso, P. Mendonça, A. Ferro, J. Pinto‐Basto, J. Coelho, F. Ferreirinha, J. Poirier, E. Parreira, Joana Vale, C. Januário, C. Barbot, A. Tuna, J. Barros, R. Koide, S. Tsuji, S. Holmes, R. Margolis, L. Jardim, M. Pandolfo, P. Coutinho, J. Sequeiros (2002)
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus.Archives of neurology, 59 4
Greg Ewing, Allen Rodrigo (2007)
Estimating population parameters using the structured serial coalescent with Bayesian MCMC inference when some demes are hidden.Evolutionary Bioinformatics, 2
K. Mizushima, M. Watanabe, I. Kondo, K. Okamoto, M. Shizuka, K. Abe, M. Aoki, M. Shoji (1999)
Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1- 2 polymorphism and contribution to founder effectJournal of Medical Genetics, 36
M. Fernandez, M. McClain, R. Martinez, K. Snow, H. Lipe, J. Ravits, T. Bird, A. Spada (2000)
Late-onset SCA2Neurology, 55
Sandra Martins, F. Calafell, V. Wong, J. Sequeiros, A. Amorim (2006)
A multistep mutation mechanism drives the evolution of the CAG repeat at MJD/SCA3 locusEuropean Journal of Human Genetics, 14
D. Shan, B. Soong, Changming Sun, S. Lee, K. Liao, R. Liu (2001)
Spinocerebellar ataxia type 2 presenting as familial levodopa‐responsive parkinsonismAnnals of Neurology, 50
S. Pulst, A. Nechiporuk, T. Nechiporuk, S. Gispert, Xiao-Ning Chen, Í. Lopes-Cendes, Susan Pearlman, S. Starkman, Guillermo Orozco-Díaz, A. Lunkes, P. Dejong, G. Rouleau, G. Auburger, J. Korenberg, C. Figueroa, S. Sahba (1996)
Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2Nature Genetics, 14
N. Wadia, R. Swami (1971)
A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families).Brain : a journal of neurology, 94 2
G. Orozco, R. Estrada, T. Perry, J. Arana, R. Fernández, A. González-Quevedo, J. Galarraga, S. Hansen (1989)
Dominantly inherited olivopontocerebellar atrophy from eastern Cuba Clinical, neuropathological, and biochemical findingsJournal of the Neurological Sciences, 93
D. Shan, Ren-Shyan Liu, Chen-Ming Sun, Shwn-Jen Lee, K. Liao, B. Soong (2004)
Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: Clinical implicationsMovement Disorders, 19
A. Filla, C. Mariotti, G. Caruso, G. Coppola, S. Cocozza, I. Castaldo, O. Calabrese, E. Salvatore, G. Michele, M. Riggio, D. Pareyson, C. Gellera, S. Donato (2000)
Relative Frequencies of CAG Expansions in Spinocerebellar Ataxia and Dentatorubropallidoluysian Atrophy in 116 Italian FamiliesEuropean Neurology, 44
O. Didierjean, G. Cancel, G. Stevanin, A. Dürr, K. Bürk, A. Benomar, A. Lézin, S. Belal, Myriem Abada-Bendid, T. Klockgether, A. Brice (1999)
Linkage disequilibrium at the SCA2 locusJournal of Medical Genetics, 36
Excoffier (2005)
Arlequin ver. 3.0: An integrated software package for population genetics data analysisEvol Bioinform Online, 1
A. Bhattacharyya, A. Thakur, Veronique Chellgren, Geetha Thiagarajan, Angela Williams, Brian Chellgren, T. Creamer, R. Wetzel (2006)
Oligoproline effects on polyglutamine conformation and aggregation.Journal of molecular biology, 355 3
The spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by gait and limb ataxia. This disease is caused by the expansion of a (CAG)n located in the ATXN2, that encodes a polyglutamine tract of more than 34 repeats. Lately, alleles with 32–33 CAGs have been associated to late‐onset disease cases. Repeat interruptions by CAA triplets are common in normal alleles, while expanded alleles usually contain a pure repeat tract. To investigate the mutational origin and the instability associated to the ATXN2 repeat, we performed an extensive haplotype study and sequencing of the CAG/CAA repeat, in a cohort of families of different geographic origins and phenotypes. Our results showed (1) CAA interruptions also in expanded ATXN2 alleles; (2) that pathological CAA interrupted alleles shared an ancestral haplotype with pure expanded alleles; and (3) higher genetic diversity in European SCA2 families, suggesting an older European ancestry of SCA2. In conclusion, we found instability towards expansion in interrupted ATXN2 alleles and a shared ancestral ATXN2 haplotype for pure and interrupted expanded alleles; this finding has strong implications in mutation diagnosis and counseling. Our results indicate that interrupted alleles, below the pathological threshold, may be a reservoir of mutable alleles, prone to expansion in subsequent generations, leading to full disease mutation. © 2009 Wiley‐Liss, Inc.
American Journal of Medical Genetics part B – Wiley
Published: Mar 1, 2010
Keywords: trinucleotide repeat expansion; polyglutamine; repeat interruptions; ancestral haplotype
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.