title: Exome sequencing in a family with restless legs syndrome.
abstract: BACKGROUND
  Restless legs syndrome (RLS) has a high familial aggregation. To date, several loci and genetic risk factors have been identified, but no causative gene mutation has been found.
  
  
  METHODS
  We evaluated a German family with autosomal dominantly inherited RLS in 7 definitely and 2 possibly affected members by genome-wide linkage analysis and exome sequencing.
  
  
  RESULTS
  We identified three novel missense and one splice site variant in the PCDHA3, WWC2, ATRN, and FAT2 genes that segregated with RLS in the family. All four exons of the PCDHA3 gene, the most plausible candidate, were sequenced in 64 unrelated RLS cases and 250 controls. This revealed three additional rare missense variants (frequency <1%) of unknown pathogenicity in 2 patients and 1 control.
  
  
  CONCLUSIONS
  We present the first next-generation sequencing study on RLS and suggest PCDHA3 as a candidate gene for RLS.
authors.affiliation: Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Weissbach
authors.forename: Katharina
authors.initials: K
authors.lastname: Siegesmund
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Irene
authors.initials: I
authors.lastname: Pichler
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Muhle
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Thora
authors.initials: T
authors.lastname: Lohnau
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schwinger
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005858:Germany; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D012148:Restless Legs Syndrome / Q000235:genetics*; D012307:Risk Factors; D015534:Trans-Activators
chemical_list: C492192:ATRN protein, human; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C502404:FAT2 protein, human; D008565:Membrane Proteins; D015534:Trans-Activators; C106908:WBP2 protein, human