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Whole-exome sequencing reveals PSEN1 and ATP7B combined variants as a possible cause of early-onset Lewy body dementia: a case study of genotype–phenotype correlation

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Abstract

Dementia with Lewy bodies is a neurodegenerative disease, sharing features with Parkinson’s and Alzheimer’s diseases. We report a case of a patient dementia with Lewy bodies carrying combined PSEN1 and ATP7B mutations. A man developed dementia with Lewy bodies starting at the age of 60 years. CSF biomarkers were of Alzheimer’s disease and DaTSCAN was abnormal. Whole-exome sequencing revealed a heterozygous p.Ile408Thr PSEN1 variant and a homozygous p.Arg616Trp ATP7B variant. This case reinstates the need of considering ATP7B mutations when evaluating a patient with parkinsonism and supports p.Ile408Thr as a pathogenic PSEN1 variant.

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Funding

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG067426. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. José Brás and Isabel Santana contributed equally to this work.

Authors and Affiliations

  1. Neurology Department, Centro Hospitalar E Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-045, Coimbra, Portugal

    Miguel Tábuas-Pereira & Isabel Santana

  2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Miguel Tábuas-Pereira & Isabel Santana

  3. Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal

    Miguel Tábuas-Pereira, Maria Rosário Almeida & Isabel Santana

  4. Centro Académico Clínico de Coimbra, University of Coimbra, Coimbra, Portugal

    Miguel Tábuas-Pereira & Isabel Santana

  5. Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA

    Rita Guerreiro, Célia Kun-Rodrigues & José Brás

  6. Division of Psychiatry and Behavioral Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, USA

    Rita Guerreiro & José Brás

  7. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Maria Rosário Almeida

Authors
  1. Miguel Tábuas-Pereira
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  2. Rita Guerreiro
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  3. Célia Kun-Rodrigues
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  4. Maria Rosário Almeida
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Correspondence to Miguel Tábuas-Pereira.

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Tábuas-Pereira, M., Guerreiro, R., Kun-Rodrigues, C. et al. Whole-exome sequencing reveals PSEN1 and ATP7B combined variants as a possible cause of early-onset Lewy body dementia: a case study of genotype–phenotype correlation. Neurogenetics 23, 279–283 (2022). https://doi.org/10.1007/s10048-022-00699-0

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  • DOI: https://doi.org/10.1007/s10048-022-00699-0

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