A TRAPPC6B splicing variant associates to restless legs syndrome

作者：Aridon Paolo; De Fusco Maurizio; Winkelmann Juliane W; Zucconi Marco; Arnao Valentina; Ferini Strambi Luigi; Casari Giorgio^*

来源：Parkinsonism & Related Disorders, 2016, 31: 135-138.

DOI：10.1016/j.parkreldis.2016.08.016

• Restless legs syndrome
• Exome sequencing
• Variation
• Splicing
• Movement disorders
• Sleep disorders
• Authors report no disclosures

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.

• 出版日期2016-10