Exome sequencing in a family with restless legs syndrome§


  • Funding agencies: This work was supported by the Volkswagen Foundation, the Hermann and Lilly Schilling Foundation, the German Research Foundation (DFG, KA3729/2-1), and inramural funding of the University of Lübeck “Schwerpunktprogramm: Medizinische Genetik - Von seltenen Varianten zur Krankheitsentstehung”

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.



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.


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.


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.


We present the first next-generation sequencing study on RLS and suggest PCDHA3 as a candidate gene for RLS. © 2012 Movement Disorder Society