Trinucleotide Repeats Number in SCA2, SCA3, and SCA17 in Early-Onset Parkinson's Disease

Background: Abnormal expansion of trinucleotide repeats in genes causing spinocerebellar ataxias such as SCA2, SCA3, SCA8, or SCA17 was reported in sporadic or familial Parkinson’s disease. Genetic factors play an important role especially in early-onset Parkinson’s disease (EOPD). To investigate mutations of ATXN2, ATXN3, and TBP as a possible cause in Korean EOPD, we analyzed mutations in these genes. We also investgated the possibility that trinucleotide repeats numbers in these genes contribute to the development of EOPD. Methods: Mutation analysis of ATXN2, ATXN3, and TBP was done in 153 EOPD defined as age-at-onset before 51. Distribution of CAG repeats numbers were compared between EOPD and age- and sex-matched controls. Results: No patients with EOPD had CAG repeats numbers in ATXN2, ATXN3, and TBP in mutation range. There was no difference in the distribution of CAG repeats between EOPD and controls, although we found a trend that CAG repeats numbers in ATXN3 appear larger in EOPD than in controls. Conclusions: Mutations of genes causing SCA2, SCA3, or SCA17 may not be a common genetic cause in Korean EOPD.

[1]  Yu Kyeong Kim,et al.  Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism. , 2007, Archives of neurology.

[2]  S. Tsuji,et al.  Polyglutamine disease: Recent advances in the neuropathology of dentatorubral‐pallidoluysian atrophy , 2006, Neuropathology : official journal of the Japanese Society of Neuropathology.

[3]  Yi Zhao,et al.  Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease , 2006, Neuroscience Letters.

[4]  T. Klockgether,et al.  Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6. , 2005, Archives of neurology.

[5]  D. Hernandez,et al.  Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: Evidence of SCA-2 expansion in a family with autosomal dominant Parkinson's disease , 2005, Neuroscience Letters.

[6]  K. Gwinn‐Hardy,et al.  Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases , 2005, Journal of Neural Transmission.

[7]  Ren-Shyan Liu,et al.  Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: Clinical implications , 2004, Movement disorders : official journal of the Movement Disorder Society.

[8]  N W Wood,et al.  Trinucleotide repeats and neurodegenerative disease. , 2004, Brain : a journal of neurology.

[9]  T. Yen,et al.  The parkinsonian phenotype of spinocerebellar ataxia type 3 in a Taiwanese family. , 2004, Parkinsonism & related disorders.

[10]  P. Lockhart,et al.  Profile of families with parkinsonism‐predominant spinocerebellar ataxia type 2 (SCA2) , 2004, Movement disorders : official journal of the Movement Disorder Society.

[11]  K. Gwinn‐Hardy,et al.  Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease , 2004, Clinical genetics.

[12]  M. Oda,et al.  Possible reduced penetrance of expansion of 44 to 47 CAG/CAA repeats in the TATA-binding protein gene in spinocerebellar ataxia type 17. , 2004, Archives of neurology.

[13]  Karen Marder,et al.  Familial aggregation of early‐ and late‐onset Parkinson's disease , 2003, Annals of neurology.

[14]  V. Kostic,et al.  SCA2 and SCA3 mutations in young‐onset dopa‐responsive parkinsonism , 2003, European journal of neurology.

[15]  Willibald Gerschlager,et al.  Chronic thalamic stimulation in a patient with spinocerebellar ataxia type 2 , 2003, Movement disorders : official journal of the Movement Disorder Society.

[16]  P. Lockhart,et al.  SCA-2 presenting as parkinsonism in an Alberta family , 2002, Neurology.

[17]  K. Marder,et al.  Role of SCA2 mutations in early‐ and late‐onset dopa‐responsive parkinsonism , 2002, Annals of neurology.

[18]  S. Tsuji,et al.  Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. , 2002, Archives of neurology.

[19]  B. Jeon,et al.  Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. , 2001, Molecules and cells.

[20]  Changming Sun,et al.  Spinocerebellar ataxia type 2 presenting as familial levodopa‐responsive parkinsonism , 2001, Annals of neurology.

[21]  C. Broeckhoven,et al.  CAG repeat expansion in the TATA box-binding protein gene causes autosomal dominant cerebellar ataxia. , 2001, Brain : a journal of neurology.

[22]  I. Kanazawa,et al.  SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. , 2001, Human molecular genetics.

[23]  P. Vieregge,et al.  Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia , 2001, European Journal of Human Genetics.

[24]  M. Farrer,et al.  Spinocerebellar ataxia type 3 phenotypically resembling parkinson disease in a black family. , 2001, Archives of neurology.

[25]  S. Tsuji,et al.  Pathology of CAG repeat diseases , 2000, Neuropathology : official journal of the Japanese Society of Neuropathology.

[26]  M. Farrer,et al.  Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese , 2000, Neurology.

[27]  B. Jeon,et al.  Spinocerebellar ataxia type 2 in seven Korean families: CAG trinucleotide expansion and clinical characteristics. , 1999, Journal of Korean medical science.

[28]  Georg Auburger,et al.  Spinocerebellar ataxia 2 (SCA2): morphometric analyses in 11 autopsies , 1999, Acta Neuropathologica.

[29]  J W Langston,et al.  Parkinson disease in twins: an etiologic study. , 1999, JAMA.

[30]  G. Rouleau,et al.  Fluorodopa and raclopride PET analysis of patients with Machado-Joseph disease , 1997, Neurology.

[31]  P. S. St George-Hyslop,et al.  Dopa‐responsive parkinsonism phenotype of Machado‐Joseph disease: Confirmation of 14q CAG expansion , 1995, Annals of neurology.

[32]  C. S. Lu,et al.  Genetic and DAT imaging studies of familial parkinsonism in a Taiwanese cohort. , 2006, Journal of neural transmission. Supplementum.

[33]  K. Gwinn‐Hardy When is ataxia not ataxia? , 2004, Archives of neurology.

[34]  Hsiu-Chen Chang,et al.  The parkinsonian phenotype of spinocerebellar ataxia type 2. , 2004, Archives of neurology.

[35]  小出 玲爾,et al.  A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene : a new polyglutamine disease? , 2000 .

[36]  D. Borchelt,et al.  Polyglutamine pathogenesis. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.