1. A TRAPPC6B splicing variant associates to restless legs syndrome
- Author
-
Valentina Arnao, Juliane Winkelmann, Luigi Ferini-Strambi, Paolo Aridon, Giorgio Casari, Marco Zucconi, Maurizio De Fusco, Aridon, P., De Fusco, M., Winkelmann, J., Zucconi, M., Arnao, V., Ferini-Strambi, L., Casari, G., Aridon, Paolo, De Fusco, Maurizio, Winkelmann, Juliane W., Zucconi, Marco, Arnao, Valentina, FERINI STRAMBI, Luigi, and Casari, GIORGIO NEVIO
- Subjects
0301 basic medicine ,Exome sequencing ,Male ,Vesicular Transport Proteins ,Locus (genetics) ,Variation ,Gene mutation ,Biology ,Splicing ,Transfection ,03 medical and health sciences ,Exon ,Gene Frequency ,RLS ,Restless Legs Syndrome ,Animals ,Humans ,Genetic Predisposition to Disease ,RNA, Messenger ,Restless legs syndrome ,Exome ,Movement disorder ,Cells, Cultured ,Genetics ,Chromosomes, Human, Pair 14 ,Family Health ,Sleep disorder ,Haplotype ,Exons ,Rats ,030104 developmental biology ,Authors report no disclosure ,Neurology ,Haplotypes ,RNA splicing ,Mutation ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Neurological disease ,Minigene - 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.
- Published
- 2016