, Volume 14, Issue 1, pp 53–61 | Cite as

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

  • Larissa ArningEmail author
  • Jörg T. Epplen
  • Elisa Rahikkala
  • Corinna Hendrich
  • Albert C. Ludolph
  • Anne-Dorte Sperfeld
Short Communication


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.


SETX·amyotrophic lateral sclerosis ALS4 Ataxia AOA2 Missense mutations 



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


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Larissa Arning
    • 1
    Email author
  • Jörg T. Epplen
    • 1
  • Elisa Rahikkala
    • 2
  • Corinna Hendrich
    • 3
    • 5
  • Albert C. Ludolph
    • 3
  • Anne-Dorte Sperfeld
    • 3
    • 4
  1. 1.Department of Human GeneticsRuhr UniversityBochumGermany
  2. 2.Department of Clinical Genetics, Oulu University HospitalUniversity of OuluOuluFinland
  3. 3.Department of NeurologyUniversity of UlmUlmGermany
  4. 4.Neurologische KlinikIbbenbürenGermany
  5. 5.Neurologische KlinikKemptenGermany

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