title: A TRAPPC6B splicing variant associates to restless legs syndrome.
abstract: RLS is a common movement disorders with a strong genetic component in its pathophysiology, but, up to now, no causative mutation has been reported.
  
  
  
  We re-evaluated the previously described RLS2 family by exome sequencing.
  
  
  
  We identified fifteen variations in the 14q critical region. The c.485G > A transition of the TRAPPC6B gene segregates with the RLS2 haplotype, is absent in 200 local controls and is extremely rare in 12988 exomes from the Exome Variant Server (EVS). This variant alters a splicing site and hampers the normal transcript processing by promoting exon 3-skipping as demonstrated by minigene transfection and by patient transcripts.
  
  
  
  We identified a TRAPPC6B gene mutation associated to the RLS locus on chromosome 14.
authors: Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy; Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche-BioNec, Università di Palermo, Palermo, Italy.
authors: Paolo
authors: P
authors: Aridon
authors: Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors: Maurizio
authors: M
authors: De Fusco
authors: Institut für Neurogenomik, Helmholtz Zentrum München, Munich, Germany; Neurologische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors: Juliane W
authors: JW
authors: Winkelmann
authors: Sleep Disorders Center, Department of Clinical Neurosciences, Vita-Salute San Raffaele University, San Raffaele-Turro Hospital, Milan, Italy.
authors: Marco
authors: M
authors: Zucconi
authors: Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche-BioNec, Università di Palermo, Palermo, Italy.
authors: Valentina
authors: V
authors: Arnao
authors: Sleep Disorders Center, Department of Clinical Neurosciences, Vita-Salute San Raffaele University, San Raffaele-Turro Hospital, Milan, Italy.
authors: Luigi
authors: L
authors: Ferini-Strambi
authors: Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy. Electronic address: casari.giorgio@hsr.it.
authors: Giorgio
authors: G
authors: Casari
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005091:Exons; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012148:Restless Legs Syndrome / Q000235:genetics*; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C506759:TRAPPC6B protein, human; D033921:Vesicular Transport Proteins
keywords: Authors report no disclosures; Exome sequencing; Movement disorders; Restless legs syndrome; Sleep disorders; Splicing; Variation