Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families.
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.
Ishihara
Lianna
L
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. lsi20@medschl.com.ac.uk
Gibson
Rachel A
RA
Warren
Liling
L
Amouri
Rim
R
Lyons
Kelly
K
Wielinski
Catherine
C
Hunter
Christine
C
Swartz
Jina E
JE
Elango
Ramu
R
Akkari
P Anthony
PA
Leppert
David
D
Surh
Linda
L
Reeves
Kevin H
KH
Thomas
Siwan
S
Ragone
Leigh
L
Hattori
Nobutaka
N
Pahwa
Rajesh
R
Jankovic
Joseph
J
Nance
Martha
M
Freeman
Alan
A
Gouider-Khouja
Neziha
N
Kefi
Mounir
M
Zouari
Mourad
M
Ben Sassi
Samia
S
Ben Yahmed
Samia
S
El Euch-Fayeche
Ghada
G
Middleton
Lefkos
L
Burn
David J
DJ
Watts
Ray L
RL
Hentati
Faycal
F
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
D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine