title: The PD-associated alpha-synuclein promoter Rep1 allele 2 shows diminished frequency in restless legs syndrome.
abstract: Gain-of-function mutations of alpha-synuclein (SNCA) are known to trigger Parkinson's disease (PD) with striatal dopaminergic deficits and a reduction of spontaneous movements. The longest size variant (allele 2) of the complex microsatellite repeat Rep1 within the SNCA gene promoter is known to confer a PD risk. We now observed this Rep1 allele 2 to show significantly decreased frequency in restless legs syndrome (RLS) in a genotyping study of 258 patients versus 235 healthy controls from Germany. Given that RLS is a disease with increased spontaneous movements and with increased striatal dopamine signaling, these novel data appear plausible. The scarcity of this alpha-synuclein gain-of-function variant in RLS might suggest that a low alpha-synuclein function via the SNARE complex in presynaptic vesicle release and neurotransmission of the striatum contributes to RLS pathogenesis.
authors.affiliation: Neurodegeneration Research Laboratory, Molecular Biology and Genetics Department, Bogazici University, 34342, Istanbul, Turkey.
authors.forename: Suna
authors.initials: S
authors.lastname: Lahut
authors.forename: David
authors.initials: D
authors.lastname: Vadasz
authors.forename: Candan
authors.initials: C
authors.lastname: Depboylu
authors.forename: Vincent
authors.initials: V
authors.lastname: Ries
authors.forename: Martina
authors.initials: M
authors.lastname: Krenzer
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny-Kolster
authors.forename: A Nazli
authors.initials: AN
authors.lastname: Basak
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005787:Gene Frequency; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012148:Restless Legs Syndrome / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein