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Machado Joseph-Disease Is Rare in the Peruvian Population

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Abstract

Spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD/SCA3) is the most prevalent autosomal dominant cerebellar ataxia worldwide, but its frequency varies by geographic region. We describe MJD/SCA3 patients diagnosed in a tertiary healthcare institution in Peru. In a cohort of 341 individuals (253 probands) with clinical ataxia diagnosis, seven MJD/SCA3 probands were identified and their pedigrees extended, detecting a total of 18 MJD/SCA3 cases. Out of 506 alleles from all probands from this cohort, the 23-CAG repeat was the most common ATXN3 allele (31.8%), followed by the 14-CAG repeat allele (26.1%). Normal alleles ranged from 12 to 38 repeats while pathogenic alleles ranged from 64 to 75 repeats. We identified 80 large normal (LN) alleles (15.8%). Five out of seven families declared an affected family member traced back to foreign countries (England, Japan, China, and Trinidad and Tobago). MJD/SCA3 patients showed ataxia, accompanied by pyramidal signs, dysarthria, and dysphagia as well as abnormal oculomotor movements. In conclusion, ATXN3 allelic distribution in non-MJD/SCA3 patients with ataxia is similar to the distribution in normal individuals around the world, whereas LN allele frequency reinforces no correlation with the frequency of MJD/SCA3. Evidence of any atypical MJD/SCA3 phenotype was not found. Furthermore, haplotypes are required to confirm the foreign origin of MJD/SCA3 in the Peruvian population.

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The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

We are grateful to Victoria Marca-Ysabel, Miguel Inca-Martínez, and Diego Veliz-Otani for logistic support and lab assistance; Melissa Moleros for her assistance on recruitment of participants; and Lucy Stirland for her review of the manuscript. We are grateful to the DNA-Neurogenetics Bank of the Instituto Nacional de Ciencias Neurológicas for supporting the collection of DNA samples and associated data used in this publication. Samples from the DNA-Neurogenetics Bank were obtained through informed consent and IRB approval. The content in this publication does not reflect the opinion of the DNA-Neurogenetics Bank.

Funding

This study was funded by the Peruvian Institution PROCIENCIA-CONCYTEC within the framework of the convention of Research Projects in Health EU-LAC (Contract No. 098–2017-FONDECYT). Authors affiliated to Instituto National de Ciencias Neurológicas are also partially supported by Contract No. 148–2020-PROCIENCIA.

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Authors and Affiliations

  1. Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru

    Mario Cornejo-Olivas, Lesly Solis-Ponce, Ismael Araujo-Aliaga, Karina Milla-Neyra, Olimpio Ortega, Maryenela Illanes-Manrique, Pilar Mazzetti, Carla Manrique-Enciso, Diana Cubas-Montecino & Elison Sarapura-Castro

  2. Carrera de Medicina Humana, Universidad Científica del Sur, Lima, Peru

    Mario Cornejo-Olivas

  3. Instituto Nacional de Salud, Lima, Peru

    Lesly Solis-Ponce

  4. Global Brain Health Institute, University of California, San Francisco, CA, USA

    Maryenela Illanes-Manrique

  5. Universidad Nacional Mayor de San Marcos, Lima, Peru

    Pilar Mazzetti

  6. Serviço de Genética Médica e Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Maria Luiza Saraiva-Pereira & Laura B. Jardim

  7. Deptos. de Bioquímica e Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Maria Luiza Saraiva-Pereira & Laura B. Jardim

Authors
  1. Mario Cornejo-Olivas
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  10. Maria Luiza Saraiva-Pereira
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  11. Laura B. Jardim
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  12. Elison Sarapura-Castro
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Contributions

All authors read and approved the final manuscript. All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Lesly Solis-Ponce, Elison Sarapura-Castro, Karina Milla-Neyra, Maryenela Illanes-Manrique, Pilar Mazzetti, Ismael Araujo-Aliaga, Olimpio Ortega, Carla Manrique-Enciso, Diana Cubas-Montecino, Maria Luiza Saraiva-Pereira, Laura B. Jardim, and Mario Cornejo-Olivas. The first draft of the manuscript was written by Ismael Araujo-Aliaga, Lesly Solis-Ponce, and Mario Cornejo-Olivas, and all authors commented on later versions of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Mario Cornejo-Olivas.

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Ethical Approval

The study was approved by the Ethics Committee at INCN, called the “Comité Institucional de Ética en Investigación del Instituto Nacional de Ciencias Neurológicas,” IRB number 486–2018-CIEI-INCN. All patients provided written informed consent for use of their genetic and clinical data for anonymized research studies at the time of their genetic testing. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

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Cornejo-Olivas, M., Solis-Ponce, L., Araujo-Aliaga, I. et al. Machado Joseph-Disease Is Rare in the Peruvian Population. Cerebellum 22, 1192–1199 (2023). https://doi.org/10.1007/s12311-022-01491-4

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