title: Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families.
abstract: Mutations in the leucine-rich repeat kinase-2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G > A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. lsi20@medschl.com.ac.uk
authors.forename: Lianna
authors.initials: L
authors.lastname: Ishihara
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Gibson
authors.forename: Liling
authors.initials: L
authors.lastname: Warren
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.forename: Kelly
authors.initials: K
authors.lastname: Lyons
authors.forename: Catherine
authors.initials: C
authors.lastname: Wielinski
authors.forename: Christine
authors.initials: C
authors.lastname: Hunter
authors.forename: Jina E
authors.initials: JE
authors.lastname: Swartz
authors.forename: Ramu
authors.initials: R
authors.lastname: Elango
authors.forename: P Anthony
authors.initials: PA
authors.lastname: Akkari
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.forename: Linda
authors.initials: L
authors.lastname: Surh
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Reeves
authors.forename: Siwan
authors.initials: S
authors.lastname: Thomas
authors.forename: Leigh
authors.initials: L
authors.lastname: Ragone
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pahwa
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Martha
authors.initials: M
authors.lastname: Nance
authors.forename: Alan
authors.initials: A
authors.lastname: Freeman
authors.forename: Neziha
authors.initials: N
authors.lastname: Gouider-Khouja
authors.forename: Mounir
authors.initials: M
authors.lastname: Kefi
authors.forename: Mourad
authors.initials: M
authors.lastname: Zouari
authors.forename: Samia
authors.initials: S
authors.lastname: Ben Sassi
authors.forename: Samia
authors.initials: S
authors.lastname: Ben Yahmed
authors.forename: Ghada
authors.initials: G
authors.lastname: El Euch-Fayeche
authors.forename: Lefkos
authors.initials: L
authors.lastname: Middleton
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.forename: Ray L
authors.initials: RL
authors.lastname: Watts
authors.forename: Faycal
authors.initials: F
authors.lastname: Hentati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003431:Cross-Cultural Comparison; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009656:North America / Q000453:epidemiology / Q000208:ethnology; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology / Q000208:ethnology; D044465:White People
chemical_list: D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine