title: Genetic analysis for five LRRK2 mutations in a Sardinian parkinsonian population: importance of G2019S and R1441C mutations in sporadic Parkinson's disease patients.
abstract: Mutations in the LRRK2 gene are the most common known cause of familial and sporadic Parkinson's disease (PD). Few studies performed to date to assess frequency of these mutations are actually only representative of specific areas. Here we study the frequency and clinical phenotype of LRRK2 G2019S, I2020T and R1441C/G/H mutations in 356 Sardinian patients with idiopathic PD and 208 controls. Seventeen additional subjects, relatives of PD mutated probands, were enrolled. Eight patients were mutated in heterozygosis for LRRK2 gene (2.3%): six carried the G2019S (1.7%) and two the R1441C (0.6%) mutation. Three PD patients G2019S carriers (50%) were detected in two contiguous villages comprising 3921 inhabitants while the other three (50%) were identified in the remaining population of 796,079 inhabitants. Only one mutated proband had a family history of PD. LRRK2 G2019S and R1441C mutations associated with PD were not an uncommon mutation in a Sardinian population, especially in sporadic PD patients. The detection of the G2019S variant in ten unaffected relatives confirms a reduced penetrance of the underlying mutation and might explain its prevalence among patients with sporadic PD. These findings may provide new insights into the importance of studies of frequency of LRKK2 mutations in PD patients originating from small ethnically homogeneous populations.
authors.affiliation: Centro per i Disordini del Movimento, Dipartimento di Scienze Cardiovascolari e Neurologiche, Sezione Neurologia, University of Cagliari, Cagliari, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Floris
authors.forename: Antonino
authors.initials: A
authors.lastname: Cannas
authors.forename: Paolo
authors.initials: P
authors.lastname: Solla
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Murru
authors.forename: Stefania
authors.initials: S
authors.lastname: Tranquilli
authors.forename: Daniela
authors.initials: D
authors.lastname: Corongiu
authors.forename: Marcella
authors.initials: M
authors.lastname: Rolesu
authors.forename: Stefania
authors.initials: S
authors.lastname: Cuccu
authors.forename: Claudia
authors.initials: C
authors.lastname: Sardu
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Marrosu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007558:Italy; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D044382:Population Groups / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D012694:Serine; D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D003545:Cysteine; D005998:Glycine