title: A post hoc study on gene panel analysis for the diagnosis of dystonia.
abstract: Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis.
  
  
  
  In this post hoc study, we describe gene panel analysis results of 61 dystonia patients (mean age, 31 years; 72% young onset) in our tertiary referral center. The panel covered 94 dystonia-associated genes. As comparison with a historic cohort was not possible because of the rapidly growing list of dystonia genes, we compared the diagnostic workup with and without gene panel analysis in the same patients. The workup without gene panel analysis (control group) included theoretical diagnostic strategies formulated by independent experts in the field, based on detailed case descriptions. The primary outcome measure was diagnostic yield; secondary measures were cost and duration of diagnostic workup.
  
  
  
  Workup with gene panel analysis led to a confirmed molecular diagnosis in 14.8%, versus 7.4% in the control group (P = 0.096). In the control group, on average 3 genes/case were requested. The mean costs were lower in the gene panel analysis group (€1822/case) than in the controls (€2660/case). The duration of the workup was considerably shorter with gene panel analysis (28 vs 102 days).
  
  
  
  Gene panel analysis facilitates molecular diagnosis in complex cases of dystonia, with a good diagnostic yield (14.8%), a quicker diagnostic workup, and lower costs, representing a major improvement for patients and their families. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Neurology, Groningen, the Netherlands.|Ommelander Ziekenhuis Groningen, Department of Neurology, Delfzijl and Winschoten, the Netherlands.
authors.forename: Martje E
authors.initials: ME
authors.lastname: van Egmond
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Neurology, Groningen, the Netherlands.
authors.forename: Coen H A
authors.initials: CHA
authors.lastname: Lugtenberg
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Neurology, Groningen, the Netherlands.
authors.forename: Oebele F
authors.initials: OF
authors.lastname: Brouwer
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.|Department of Neurology, Haga Teaching Hospital, The Hague, the Netherlands.
authors.forename: Maria Fiorella
authors.initials: MF
authors.lastname: Contarino
authors.affiliation: Movement Disorders Unit, Department of Neurology, Westmead Hospital & Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Victor S C
authors.initials: VSC
authors.lastname: Fung
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Laboratory Medicine, Groningen, the Netherlands.
authors.forename: M Rebecca
authors.initials: MR
authors.lastname: Heiner-Fokkema
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Annemarie H
authors.initials: AH
authors.lastname: van der Hout
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Peall
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
authors.affiliation: Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière and Sorbonne Universités, Université Pierre and Marie Curie, Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, the Netherlands.
authors.forename: Corien C
authors.initials: CC
authors.lastname: Verschuuren-Bemelmans
authors.affiliation: Radboud University Medical Centre, Department of Paediatric Neurology, Nijmegen, the Netherlands.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Willemsen
authors.affiliation: VU University Medical Centre, Department of Child Neurology and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Neurology, Groningen, the Netherlands.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Tijssen
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Neurology, Groningen, the Netherlands.|University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, the Netherlands.|University of Groningen, University Medical Centre Groningen, Department of Paediatrics, Groningen, the Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D015331:Cohort Studies; D003365:Costs and Cost Analysis; D004252:DNA Mutational Analysis / Q000191:economics / Q000379:methods*; D004421:Dystonia / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D017063:Outcome Assessment, Health Care; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human
keywords: cost; diagnostic yield; dystonia; gene panel analysis; next-generation sequencing