Spinocerebellar Ataxias in Brazil—Frequencies and Modulating Effects of Related Genes

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• 作者：Raphael Machado de Castilhos (1) (21) (22)
  Gabriel Vasata Furtado (2) (21)
  Tailise Conte Gheno (2) (21)
  Paola Schaeffer (1)
  Aline Russo (1)
  Orlando Barsottini (3)
  José Luiz Pedroso (3)
  Diego Z. Salarini (4)
  Fernando Regla Vargas (5) (6) (7)
  Maria Angélica de Faria Domingues de Lima (6) (7)
  Clécio Godeiro (8)
  Luiz Carlos Santana-da-Silva (22) (9)
  Maria Betania Pereira Toralles (10)
  Silvana Santos (11) (22)
  Hélio van der Linden Jr (12)
  Hector Yuri Wanderley (13)
  Paula Frassineti Vanconcelos de Medeiros (14)
  Eliana Ternes Pereira (15)
  Erlane Ribeiro (16)
  Maria Luiza Saraiva-Pereira (17) (18) (21) (22)
  Laura Bannach Jardim (17) (19) (20) (21) (22)
  
• 关键词：Spinocerebellar ataxias ; SCA3/MJD ; SCA2 ; SCA7 ; SCA10 ; Modifier genes
• 刊名：The Cerebellum
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：13
• 期：1
• 页码：17-28
• 全文大小：471 KB
• 作者单位：Raphael Machado de Castilhos (1) (21) (22)
  Gabriel Vasata Furtado (2) (21)
  Tailise Conte Gheno (2) (21)
  Paola Schaeffer (1)
  Aline Russo (1)
  Orlando Barsottini (3)
  José Luiz Pedroso (3)
  Diego Z. Salarini (4)
  Fernando Regla Vargas (5) (6) (7)
  Maria Angélica de Faria Domingues de Lima (6) (7)
  Clécio Godeiro (8)
  Luiz Carlos Santana-da-Silva (22) (9)
  Maria Betania Pereira Toralles (10)
  Silvana Santos (11) (22)
  Hélio van der Linden Jr (12)
  Hector Yuri Wanderley (13)
  Paula Frassineti Vanconcelos de Medeiros (14)
  Eliana Ternes Pereira (15)
  Erlane Ribeiro (16)
  Maria Luiza Saraiva-Pereira (17) (18) (21) (22)
  Laura Bannach Jardim (17) (19) (20) (21) (22)
  
  1. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Rio Grande do Sul, Brazil
  21. Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  22. Instituto Nacional de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil
  2. Laboratory of Genetic Identification, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Rio Grande do Sul, Brazil
  3. Setor de Neurologia Geral e Ataxias. Disciplina de Neurologia Clínica da UNIFESP-Escola Paulista de Medicina, Universidade Federal de S?o Paulo, S?o Paulo, Brazil
  4. Ambulatório de Distúrbios do Movimento e Neurogenética, Disciplina de Neurologia da Santa Casa de S?o Paulo, S?o Paulo, Brazil
  5. Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
  6. Post-Graduation Program, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
  7. Genetic Counseling Program, Instituto Nacional do Cancer, Rio de Janeiro, Brazil
  8. Universidade Federal do Rio Grande do Norte, Natal, Brazil
  9. Laboratório de Erros Inatos do Metabolismo, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém do Pará, Brazil
  10. Universidade Federal da Bahia, Salvador, Brazil
  11. Universidade Estadual da Paraíba, Campina Grande, Brazil
  12. Centro de Reabilita??o Dr. Henrique Santillo, Goiania, Goiás, Brazil
  13. APAE de Vitória, Espírito Santo, Brazil
  14. Universidade Federal de Campina Grande, Paraíba, Brazil
  15. Universidade Federal de Santa Catarina, Florianópolis, Brazil
  16. Associa??o Cearense de Doen?as Genéticas, Fortaleza, Brazil
  17. Medical Genetics Service and Laboratory of Genetic Identification, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Rio Grande do Sul, Brazil
  18. Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  19. Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  20. Post-Graduation Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  
• ISSN：1473-4230

文摘

This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6?%), 28 SCA2 (7.8?%), 20 SCA7 (5.6?%), 15 SCA1 (4.2?%), 12 SCA10 (3.3?%), 5 SCA6 (1.4?%), and 65 families without a molecular diagnosis (18.1?%). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7?% of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p-lt;-.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.