title: Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants.
abstract: Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin.
authors.affiliation: Neurogenetics Unit, Department of Neurology, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Xiromerisiou
authors.forename: G M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: V
authors.initials: V
authors.lastname: Gourbali
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: I
authors.initials: I
authors.lastname: Papakonstantinou
authors.forename: A
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: A B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D006115:Greece; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases