A TRAPPC6B splicing variant associates to restless legs syndrome. (October 2016)

• Record Type: Journal Article
• Authors: Aridon, Paolo; De Fusco, Maurizio; Winkelmann, Juliane W.; Zucconi, Marco; Arnao, Valentina; Ferini-Strambi, Luigi; Casari, Giorgio
• Is Part Of: Parkinsonism & related disorders. Volume 31(2016)
• Page Start: 135
• Page End: 138
• Publication Date: 2016-10
• Subjects: Restless legs syndrome -- Exome sequencing -- Variation -- Splicing -- Movement disorders -- Sleep disorders -- Authors report no disclosures; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2016.08.016
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: RLS is a common movement disorders with a strong genetic component in its pathophysiology, but, up to now, no causative mutation has been reported. Methods: We re-evaluated the previously described RLS2 family by exome sequencing. Results: 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. Conclusions: We identified a TRAPPC6B gene mutation associated to the RLS locus on chromosome 14. Highlights: RLS is a common movement disorders with a strong genetic component. A large RLS pedigree with apparent autosomal dominant inheritance associates to chromosome 14 (RLS2 locus). By exome sequencing of the critical region genes we identified a splicing mutation in the TRAPPC6B gene. The TRAPPC6B gene variant has functional effect on transcript isoforms.