title: LRRK2 mutations and Parkinson's disease in Sardinia--A Mediterranean genetic isolate.
abstract: The Leucine-Rich Repeat Kinase 2 (LRRK2) Gly2019Ser mutation is frequent among Parkinson's disease (PD) patients from the Arab, Jewish, and Iberian populations, while another mutation, Arg1441Gly, is common in the Basque population. We studied the prevalence of these mutations in Sardinia, a Mediterranean genetic isolate with peculiar structure and similarities with the Basque population. Among 98 Sardinian PD probands we detected one heterozygous Gly2019Ser carrier. This mutation was also found in one of 55 Sardinian controls, an 85-year-old man, later shown to have a positive family history of parkinsonism. No carriers of Arg1441Gly, Arg1441Cys, or Arg1441His mutations were found among cases and controls. Our results suggest that the "Basque"LRRK2 mutation is absent or very rare in Sardinia. The Gly2019Ser mutation is present but its frequency is lower than that in Iberian, Arab, or Jewish populations. The identification of an 85-year-old, healthy Gly2019Ser carrier supports the concept that this mutation displays incomplete penetrance.
authors.affiliation: Neurology Service and Stroke Unit, General Hospital S. Michele AOB G. Brotzu, Piazzale Ricchi 1, 09134 Cagliari, Italy. giovannicossu@aob.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cossu
authors.forename: Marina
authors.initials: M
authors.lastname: van Doeselaar
authors.forename: Marcello
authors.initials: M
authors.lastname: Deriu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Melis
authors.forename: Andrea
authors.initials: A
authors.lastname: Molari
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D019683:Penetrance; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases