title: Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls.
abstract: BACKGROUND
  Rare autosomal-dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.
  
  
  METHODS
  We used high-resolution melting to screen all exons of ANO3 and GNAL for rare sequence variants in a population of 342 German individuals with mainly sporadic PTD and 376 general population controls.
  
  
  RESULTS
  We identified 2 novel missense variants in ANO3 (p.Ile833Val and p.Gly973Arg) and 1 novel missense variant in GNAL (p.Val146Met) in three different nonfamilial cases. Variant carriers presented with adult-onset dystonia involving the neck and/or face. In controls, 3 rare ANO3 missense variants (p.Tyr235Cys, p.Asn256Ser, and p.Pro893Leu) but no rare nonsynonymous GNAL variants were present.
  
  
  CONCLUSIONS
  GNAL variants seem to be a rare cause of PTD in our mainly sporadic German sample. Low frequency missense variants in ANO3 occur in both cases and controls, warranting further assessment of this gene in PTD pathogenesis.
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zech
authors.forename: Nadine
authors.initials: N
authors.lastname: Gross
authors.forename: Angela
authors.initials: A
authors.lastname: Jochim
authors.forename: Florian
authors.initials: F
authors.lastname: Castrop
authors.forename: Maria
authors.initials: M
authors.lastname: Kaffe
authors.forename: Christian
authors.initials: C
authors.lastname: Dresel
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haslinger
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics*; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D055815:Young Adult
chemical_list: C577591:ANO3 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; D044385:GTP-Binding Protein alpha Subunits; C084618:olfactory G protein subunit alpha olf
keywords: ANO3; GNAL; dystonia; gene; rare variants