Paolo Aridon1, Maurizio De Fusco2, Juliane W Winkelmann3, Marco Zucconi4, Valentina Arnao5, Luigi Ferini-Strambi4, Giorgio Casari6. 1. 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. 2. Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy. 3. 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. 4. Sleep Disorders Center, Department of Clinical Neurosciences, Vita-Salute San Raffaele University, San Raffaele-Turro Hospital, Milan, Italy. 5. Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche-BioNec, Università di Palermo, Palermo, Italy. 6. Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy. Electronic address: casari.giorgio@hsr.it.
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.
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.
Authors: Isaac Marin-Valencia; Gaia Novarino; Anide Johansen; Basak Rosti; Mahmoud Y Issa; Damir Musaev; Gifty Bhat; Eric Scott; Jennifer L Silhavy; Valentina Stanley; Rasim O Rosti; Jeremy W Gleeson; Farhad B Imam; Maha S Zaki; Joseph G Gleeson Journal: J Med Genet Date: 2017-06-16 Impact factor: 6.318
Authors: Leticia P Sanglard; Moysés Nascimento; Philipe Moriel; Jeffrey Sommer; Melissa Ashwell; Matthew H Poore; Márcio de S Duarte; Nick V L Serão Journal: BMC Genomics Date: 2018-09-25 Impact factor: 3.969