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Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

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Abstract

Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.

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Change history

  • 15 January 2020

    The original version of this article unfortunately contained some mistakes in Table 2. The additional row (just above SCA2) with the following information “SCA1, 1(1), 1, 50, 74, 24, 46 and 0/1” should be inserted.

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Acknowledgments

Authors would like to thank patients and families affected from inherited ataxias that kindly contributed to research on ataxias in Peruvian population. We would also thank Diego Veliz-Otani for critical review of the manuscript. We are grateful to RIBERMOV “Red Iberoamericana Multidisciplinar para el Estudio de los Trastornos de Movimiento” for providing the initial environment for collaborative research studies, as this one, among Latin Americans.

Funding

EPM, GVF, GBB, SLS, MLSP, and LBJ were supported by the National Council for Research and Development (CNPq), Brazil. LBJ received grants from Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE 2006-0384) and Pesquisa para o SUS/Fundo de Apoio à Pesquisa do Rio Grande do Sul, Brazil (PPSUS-FAPERGS, PROCESS 07-00832), for performing the laboratory procedures. MCO, MIM, VM, and PM are partially supported by research funds provided by Instituto Nacional de Ciencias Neurológicas.

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Authors and Affiliations

  1. Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, 1271 Ancash St, Barrios Altos, 15003, Lima, Peru

    Mario Cornejo-Olivas, Miguel Inca-Martinez, Victoria Marca & Pilar Mazzetti

  2. Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru

    Mario Cornejo-Olivas

  3. Lerner Research Institute, Genomic Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA

    Miguel Inca-Martinez

  4. Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Raphael Machado Castilhos, Gabriel Vasata Furtado, Eduardo Preusser Mattos, Giovana Bavia Bampi, Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  5. Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Raphael Machado Castilhos

  6. Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Gabriel Vasata Furtado, Eduardo Preusser Mattos, Giovana Bavia Bampi, Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  7. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Sandra Leistner-Segal, Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  8. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Maria Luiza Saraiva-Pereira

  9. Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Laura Bannach Jardim

  10. Instituto de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil

    Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

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The original version of this article was revised: The additional row (just above SCA2) with the following information “SCA1, 1(1), 1, 50, 74, 24, 46 and 0/1” were inserted.

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Cornejo-Olivas, M., Inca-Martinez, M., Castilhos, R.M. et al. Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance. Cerebellum 19, 208–215 (2020). https://doi.org/10.1007/s12311-019-01098-2

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