ORIGINAL ARTICLE MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy Julia Vodopiutz & Maria T. Schmook & Vassiliki Konstantopoulou & Barbara Plecko & Susanne Greber-Platzer & Marc Creus & Rainer Seidl & Andreas R. Janecke Received: 16 September 2014 /Revised: 15 November 2014 /Accepted: 19 November 2014 /Published online: 3 December 2014 # Springer-Verlag Berlin Heidelberg 2014 Abstract Infantile movement disorders are rare and geneti- cally heterogeneous. We set out to identify the disease-causing mutation in siblings with a novel recessive neurodegenerative movement disorder. Genetic linkage analysis and whole- exome sequencing were performed in the original family. A cohort of six unrelated patients were sequenced for further mutations in the identified candidate gene. Pathogenicity of the mutation was evaluated by in silico analyses and by structural modeling. We identified the first and homozygous mutation (p.Gly114Ala) in the Mediator subunit 20 gene (MED20) in siblings presenting with infantile-onset spasticity and childhood-onset dystonia, progressive basal ganglia de- generation, and brain atrophy. Mediator refers to an evolution- arily conserved multi-subunit RNA polymerase II co- regulatory complex. Pathogenicity of the identified missense mutation is suggested by in silico analyses, by structural modeling, and by previous reporting of mutations in four distinct Mediator subunits causing neurodegenerative pheno- types. No further MED20 mutations were detected in this study. Conclusion: We delineate a novel infantile-onset neurode- generative movement disorder and emphasize the Mediator complex as critical for normal neuronal function. Definitive proof of pathogenicity of the identified MED20 mutation will require confirmation in unrelated patients. Keywords Dystonia . Infantile neurodegeneration . Exome sequencing . Basal ganglia degeneration . Mediator complex This study is dedicated to Professor Arnold Pollak for his life work for preterm infants and for infants with inherited diseases. Communicated by Peter de Winter Electronic supplementary material The online version of this article (doi:10.1007/s00431-014-2463-7) contains supplementary material, which is available to authorized users. J. Vodopiutz (*) : V. Konstantopoulou : S. Greber-Platzer : R. Seidl Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Wien, Austria e-mail: julia.vodopiutz@meduniwien.ac.at V. Konstantopoulou e-mail: vassiliki.konstantopoulou@meduniwien.ac.at S. Greber-Platzer e-mail: susanne.greber-platzer@meduniwien.ac.at R. Seidl e-mail: rainer.seidl@meduniwien.ac.at M. T. Schmook Department of Biomedical Imaging and Image-guided Therapy, Division of Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna, Wien, Austria e-mail: maria.schmook@meduniwien.ac.at B. Plecko Division of Neuropediatrics, University Children’ s Hospital Zürich, Zurich, Switzerland e-mail: barbara.plecko@kispi.uzh.ch M. Creus Department of Chemistry, University of Basel, Basel, Switzerland e-mail: marc.creus@unibas.ch A. R. Janecke Department of Pediatrics I, Innsbruck Medical University, Innsbruck, Austria e-mail: andreas.janecke@i-med.ac.at A. R. Janecke Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria Eur J Pediatr (2015) 174:113–118 DOI 10.1007/s00431-014-2463-7