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A comprehensive clinical and genetic study of a large Mexican population with spinocerebellar ataxia type 7

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Abstract

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration. We recently described one of the largest series of patients with SCA7 that originated from a founder effect in a Mexican population, which allowed us to perform herein the first comprehensive clinical, neurophysiological, and genetic characterization of Mexican patients with SCA7. In this study, 50 patients, categorized into adult or early phenotype, were clinically assessed using standard neurological exams and genotyped using fluorescent PCR and capillary electrophoresis. Patients with SCA7 exhibited the classical phenotype of the disease characterized by cerebellar ataxia and visual loss; however, we reported, for the first time, frontal-executive disorders and altered sensory-motor peripheral neuropathy in these patients. Semiquantitative analysis of ataxia-associated symptoms was performed using Scale for the Assessment and Rating of Ataxia (SARA) and the Brief Ataxia Rating Scale (BARS) scores, while extracerebellar features were measured employing the Inventory of Non-ataxia Symptoms (INAS) scale. Ataxia rating scales confirmed the critical role size of cytosine-adenine-guanine (CAG) repeat size on age at onset and disease severity, while analysis of CAG repeat instability showed that paternal rather than maternal transmission led to greater instability.

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Acknowledgments

This work was supported by the Secretary of Science, Technology and Innovation of the Federal District (grant number PICSA12-162) to JJ-M and CONACyT fellowship 203861 to L-VP and B-C. Our paper is dedicated to the patients and the members of SCA-affected families. We also thank Hernán Cortés and Joan Jano-Ito for the technical assistance.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute (INR), Mexico City, Mexico

    L. Velázquez-Pérez, C. M. Cerecedo-Zapata, O. Hernández-Hernández, Y. S. Tapia-Guerrero, N. Leyva-García & J. J. Magaña

  2. Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Av. Instituto Politécnico Nacional No. 2508, Col. San Pedro Zacatenco, 07360, Mexico City, Mexico

    L. Velázquez-Pérez & B. Cisneros

  3. Center for Research and Rehabilitation of the Hereditary Ataxias (CIRAH), Holguín, Cuba

    L. Velázquez-Pérez & R. Rodríguez-Labrada

  4. Rehabilitation and Social Inclusion Center of Veracruz (CRIS-DIF), Xalapa, Veracruz, Mexico

    C. M. Cerecedo-Zapata, E. Martínez-Cruz, J. Salas-Vargas & R. Gurrola-Betancourth

  5. Department of Brain Plasticity, INR, Mexico City, Mexico

    R. González-Piña

Authors
  1. L. Velázquez-Pérez
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  2. C. M. Cerecedo-Zapata
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  3. O. Hernández-Hernández
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  4. E. Martínez-Cruz
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  5. Y. S. Tapia-Guerrero
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  6. R. González-Piña
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  7. J. Salas-Vargas
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  8. R. Rodríguez-Labrada
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  10. N. Leyva-García
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  11. B. Cisneros
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  12. J. J. Magaña
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Corresponding authors

Correspondence to B. Cisneros or J. J. Magaña.

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Correlation between different scales of semiquantitative assessment of cerebellar and non-ataxia symptoms. (GIF 19 kb)

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Velázquez-Pérez, L., Cerecedo-Zapata, C.M., Hernández-Hernández, O. et al. A comprehensive clinical and genetic study of a large Mexican population with spinocerebellar ataxia type 7. Neurogenetics 16, 11–21 (2015). https://doi.org/10.1007/s10048-014-0424-y

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