Journal of Neurology

, Volume 261, Issue 1, pp 207–212 | Cite as

Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation

  • Sarah Doss
  • Katja Lohmann
  • Philip Seibler
  • Björn Arns
  • Thomas Klopstock
  • Christine Zühlke
  • Karen Freimann
  • Susen Winkler
  • Thora Lohnau
  • Mario Drungowski
  • Peter Nürnberg
  • Karin Wiegers
  • Ebba Lohmann
  • Sadaf Naz
  • Meike Kasten
  • Georg Bohner
  • Alfredo Ramirez
  • Matthias Endres
  • Christine Klein
Original Communication

Abstract

DYTCA is a syndrome that is characterized by predominant dystonia and mild cerebellar ataxia. We examined two affected siblings with healthy, consanguineous, Turkish parents. Both patients presented with a combination of childhood-onset cerebellar ataxia, dystonia, and sensory axonal neuropathy. In the brother, dystonic features were most pronounced in the legs, while his sister developed torticollis. Routine diagnostic investigations excluded known genetic causes. Biochemical analyses revealed a mitochondrial respiratory chain complex IV and a coenzyme Q10 deficiency in a muscle biopsy. By exome sequencing, we identified a homozygous missense mutation (c.154A >C; p.Thr52Pro) in both patients in exon 2 of the COX20 (FAM36A) gene, which encodes a complex IV assembly factor. This variant was confirmed by Sanger sequencing, was heterozygous in both parents, and was absent from 427 healthy controls. The exact same mutation was recently reported in a patient with ataxia and muscle hypotonia. Among 128 early-onset dystonia and/or ataxia patients, we did not detect any other patient with a COX20 mutation. cDNA sequencing and semi-quantitative analysis were performed in fibroblasts from one of our homozygous mutation carriers and six controls. In addition to the exchange of an amino acid, the mutation led to a shift in splicing. In conclusion, we extend the phenotypic spectrum of a recently identified mutation in COX20 to a recessively inherited, early-onset dystonia-ataxia syndrome that is characterized by reduced complex IV activity. Further, we confirm a pathogenic role of this mutation in cerebellar ataxia, but this mutation seems to be a rather rare cause.

Keywords

COX20 FAM36A Dystonia Cerebellar ataxia Complex IV deficiency DYTCA 

Supplementary material

415_2013_7177_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 22 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sarah Doss
    • 1
  • Katja Lohmann
    • 2
  • Philip Seibler
    • 2
  • Björn Arns
    • 2
  • Thomas Klopstock
    • 3
    • 4
    • 5
  • Christine Zühlke
    • 6
  • Karen Freimann
    • 2
  • Susen Winkler
    • 2
  • Thora Lohnau
    • 2
  • Mario Drungowski
    • 7
    • 8
  • Peter Nürnberg
    • 7
    • 8
  • Karin Wiegers
    • 2
  • Ebba Lohmann
    • 9
  • Sadaf Naz
    • 10
  • Meike Kasten
    • 2
  • Georg Bohner
    • 11
  • Alfredo Ramirez
    • 2
    • 12
    • 13
  • Matthias Endres
    • 1
    • 14
    • 15
  • Christine Klein
    • 2
  1. 1.Department of NeurologyCharité-University Medicine BerlinBerlinGermany
  2. 2.Institute of NeurogeneticsUniversity of LübeckLübeckGermany
  3. 3.Department of Neurology with Friedrich-Baur-InstituteLudwig-Maximilians-UniversityMunichGermany
  4. 4.German Network for Mitochondrial Disorders (mitoNET)MunichGermany
  5. 5.DZNE, German Center for Neurodegenerative DiseasesMunichGermany
  6. 6.Institut für HumangenetikUniversität zu LübeckLübeckGermany
  7. 7.Center for Molecular Medicine Cologne, Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC)University of CologneCologneGermany
  8. 8.ATLAS Biolabs GmbHBerlinGermany
  9. 9.Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  10. 10.School of Biological SciencesUniversity of the PunjabLahorePakistan
  11. 11.Department of NeuroradiologyCharité-University Medicine BerlinBerlinGermany
  12. 12.Department of Psychiatry and PsychotherapyUniversity of BonnBonnGermany
  13. 13.Institute of Human GeneticsUniversity of BonnBonnGermany
  14. 14.Center for Stroke Research Berlin (CSB)Charité-University Medicine BerlinBerlinGermany
  15. 15.NeuroCure Cluster of ExcellenceCharité-University Medicine BerlinBerlinGermany

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