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The SETX missense variation spectrum as evaluated in patients with ALS4-like motor neuron diseases

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Abstract

Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.

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Acknowledgments

This work was supported by a grant from the Deutsche Gesellschaft für Muskelkranke e.V. (DGM).

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Author notes

  1. Anne-Dorte Sperfeld

    Present address: Neurologische Klinik, Große Str. 41, Ibbenbüren, 49477, Germany

  2. Corinna Hendrich

    Present address: Neurologische Klinik, Kempten, Germany

Authors and Affiliations

  1. Department of Human Genetics, Ruhr University, 44780, Bochum, Germany

    Larissa Arning & Jörg T. Epplen

  2. Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland

    Elisa Rahikkala

  3. Department of Neurology, University of Ulm, Ulm, Germany

    Corinna Hendrich, Albert C. Ludolph & Anne-Dorte Sperfeld

Authors
  1. Larissa Arning
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  2. Jörg T. Epplen
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  3. Elisa Rahikkala
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  4. Corinna Hendrich
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  5. Albert C. Ludolph
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  6. Anne-Dorte Sperfeld
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Correspondence to Larissa Arning.

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Arning, L., Epplen, J.T., Rahikkala, E. et al. The SETX missense variation spectrum as evaluated in patients with ALS4-like motor neuron diseases. Neurogenetics 14, 53–61 (2013). https://doi.org/10.1007/s10048-012-0347-4

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  • DOI: https://doi.org/10.1007/s10048-012-0347-4

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