Skip to main content
Log in

Accumulation of rare variants in the arylsulfatase G (ARSG) gene in task-specific dystonia

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Musician’s dystonia and writer’s cramp are examples of task-specific dystonia. Recently, the arylsulfatase G (ARSG) locus was suggested to be associated with musician’s dystonia and writer’s cramp by a genome-wide association study. To test for the presence of causal variants, the entire coding region and exon–intron boundaries of ARSG were sequenced in DNA samples from 158 musician’s dystonia patients which were collected at the University of Music, Drama, and Media (Hanover, Germany), and 72 patients with writer’s cramp which were recruited at the Academic Medical Centers in Amsterdam and Groningen, the Netherlands. The frequency of variants within ARSG was compared to publically available data at the exome variant server (EVS) from the NHLBI GO Exome Sequencing Project. We identified 11 single nucleotide variants (SNVs) in the patients including eight non-synonymous substitutions. All variants have previously been reported at EVS including two SNVs with a reported minor allele frequency <1 %. One rare missense variant, rs61999318 (p.I493T), was significantly enriched in the group of writer’s cramp patients compared to European Americans in EVS database (p = 0.0013). In patients with writer’s cramp, there was an overall enrichment for rare, protein-changing variants compared to controls (p < 0.01). In conclusion, we did not detect any conclusive mutation in ARSG. However, we showed an association with rs61999318 in patients with writer’s cramp that contributed to an overall enrichment for rare, protein-changing variants in these patients. Thus, our data provide further support for a role of ARSG variants in task-specific dystonia, especially writer’s cramp.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Albanese A, Bhatia K, Bressman SB et al (2013) Phenomenology and classification of dystonia: a consensus update. Mov Disord 28:863–873

    Article  PubMed Central  PubMed  Google Scholar 

  2. Paudel R, Hardy J, Revesz T, Holton JL, Houlden H (2012) Review: genetics and neuropathology of primary pure dystonia. Neuropathol Appl Neurobiol 38:520–534

    Article  CAS  PubMed  Google Scholar 

  3. Berman BD, Hallett M, Herscovitch P, Simonyan K (2013) Striatal dopaminergic dysfunction at rest and during task performance in writer’s cramp. Brain 136:3645–3658

    Article  PubMed Central  PubMed  Google Scholar 

  4. Rietveld AB, Leijnse JN (2013) Focal hand dystonia in musicians: a synopsis. Clin Rheumatol 32:481–486

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt A, Jabusch HC, Altenmuller E et al (2009) Etiology of musician’s dystonia: familial or environmental? Neurology 72:1248–1254

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lohmann K, Schmidt A, Schillert A et al (2014) Genome-wide association study in musician’s dystonia: a risk variant at the arylsulfatase G locus? Mov Disord 29:921–927

    Article  CAS  PubMed  Google Scholar 

  7. Thusberg J, Olatubosun A, Vihinen M (2011) Performance of mutation pathogenicity prediction methods on missense variants. Hum Mutat 32:358–368

    Article  PubMed  Google Scholar 

  8. Steeves TD, Day L, Dykeman J, Jette N, Pringsheim T (2012) The prevalence of primary dystonia: a systematic review and meta-analysis. Mov Disord 27:1789–1796

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank M. Boerrigter for practical assistance, R.J. Sinke for critically reviewing the manuscript, and J. Senior for editing of the manuscript. This work was supported by funding from the German Research Foundation (DFG) to KL (LO 1555/4-1) and from the Prinses Beatrix Fund (WAR08-06) to MAT.

Conflicts of interest

None of the authors has any conflict of interest.

Ethical standard

The study has been approved by the appropriate ethics committees and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katja Lohmann.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 21.1 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nibbeling, E., Schaake, S., Tijssen, M.A. et al. Accumulation of rare variants in the arylsulfatase G (ARSG) gene in task-specific dystonia. J Neurol 262, 1340–1343 (2015). https://doi.org/10.1007/s00415-015-7718-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7718-3

Keywords

Navigation