title: Accumulation of rare variants in the arylsulfatase G (ARSG) gene in task-specific dystonia.
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.
authors.affiliation: Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Nibbeling
authors.forename: Susen
authors.initials: S
authors.lastname: Schaake
authors.forename: Marina A
authors.initials: MA
authors.lastname: Tijssen
authors.forename: Anne
authors.initials: A
authors.lastname: Weissbach
authors.forename: Justus L
authors.initials: JL
authors.lastname: Groen
authors.forename: Eckart
authors.initials: E
authors.lastname: Altenmüller
authors.forename: Dineke S
authors.initials: DS
authors.lastname: Verbeek
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
mesh_terms: D001192:Arylsulfatases / Q000235:genetics*; D016208:Databases, Factual / Q000706:statistics & numerical data; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D008297:Male; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C476553:ARSG protein, human; D001192:Arylsulfatases
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