E P de Mattos1, V B Leotti2, B-W Soong3, M Raposo4, M Lima4, J Vasconcelos5, H Fussiger6, G N Souza7, N Kersting7, G V Furtado1, J A M Saute7,8, S A Camey2, M L Saraiva-Pereira1,8,9, L B Jardim1,7,8,10. 1. Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul. 2. Departamento de Estatística, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. 3. Department of Neurology, Shuang Ho Hospital, Taipei Medical University School of Medicine, Taipei, Taiwan. 4. Faculdade de Ciências e Tecnologia, Universidade dos Açores, Ponta Delgada, Açores. 5. Serviço de Neurologia, Hospital do Divino Espirito Santo (HDES), Ponta Delgada, Açores, Portugal. 6. Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul. 7. Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul. 8. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul. 9. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul. 10. Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Abstract
BACKGROUND AND PURPOSE: In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the length of CAG repeat expansions in ATXN3 shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA3/MJD carriers from distinct origins and developed population-specific models to predict AO. METHODS: This was a parametric survival modelling study. RESULTS: The European formula (EF) was tested in 739 independent SCA3/MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population-specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population-specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azorean patients. Hence, specific prediction models were required for each SCA3/MJD ethnic group. CONCLUSIONS: Our data strongly support the existence of as yet unknown factors that modulate AO in SCA3/MJD in a population-dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA3/MJD carriers from distinct geographical origins.
BACKGROUND AND PURPOSE: In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the length of CAG repeat expansions in ATXN3 shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA3/MJD carriers from distinct origins and developed population-specific models to predict AO. METHODS: This was a parametric survival modelling study. RESULTS: The European formula (EF) was tested in 739 independent SCA3/MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population-specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population-specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azoreanpatients. Hence, specific prediction models were required for each SCA3/MJD ethnic group. CONCLUSIONS: Our data strongly support the existence of as yet unknown factors that modulate AO in SCA3/MJD in a population-dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA3/MJD carriers from distinct geographical origins.
Authors: Shi-Rui Gan; Karla P Figueroa; Hao-Ling Xu; Susan Perlman; George Wilmot; Christopher M Gomez; Jeremy Schmahmann; Henry Paulson; Vikram G Shakkottai; Sarah H Ying; Theresa Zesiewicz; Khalaf Bushara; Michael D Geschwind; Guangbin Xia; S H Subramony; Liana Rosenthal; Tetsuo Ashizawa; Stefan M Pulst; Ning Wang; Sheng-Han Kuo Journal: Parkinsonism Relat Disord Date: 2020-02-17 Impact factor: 4.891
Authors: Roberto Rodríguez-Labrada; Ana Carolina Martins; Jonathan J Magaña; Yaimeé Vazquez-Mojena; Jacqueline Medrano-Montero; Juan Fernandez-Ruíz; Bulmaro Cisneros; Helio Teive; Karen N McFarland; Maria Luiza Saraiva-Pereira; César M Cerecedo-Zapata; Christopher M Gomez; Tetsuo Ashizawa; Luis Velázquez-Pérez; Laura Bannach Jardim Journal: Cerebellum Date: 2020-06 Impact factor: 3.847
Authors: Gabriel Vasata Furtado; Camila Maria de Oliveira; Gabriela Bolzan; Jonas Alex Morales Saute; Maria Luiza Saraiva-Pereira; Laura Bannach Jardim Journal: Genet Mol Biol Date: 2019-06-10 Impact factor: 1.771