Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations.
BACKGROUND
The G2019S mutation is the most common pathogenic substitution in the leucine-rich repeat kinase 2 (LRRK2) gene, which has recently been identified in familial and sporadic Parkinson disease (PD).


OBJECTIVE
To report the clinical characteristics of PD patients with homozygous LRRK2 6055G>A (G2019S) mutations and to compare them with previously published descriptions of heterozygous patients.


METHODS
Descriptive clinical report from an international consortium of studies. Subjects Patients with familial PD and homozygous LRRK2 mutations included 23 Tunisians, 2 Algerians, 2 US patients, 1 Canadian, and 1 Moroccan.


RESULTS
There were no observable differences between the homozygote and heterozygote phenotypes.


CONCLUSIONS
Parkinson disease related to LRRK2 is characterized by typical clinical features, and the similarities between patients with homozygous and heterozygous mutations do not support a gene dosage effect.
Ishihara
Lianna
L
Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
Warren
Liling
L
Gibson
Rachel
R
Amouri
Rim
R
Lesage
Suzanne
S
Dürr
Alexandra
A
Tazir
Meriem
M
Wszolek
Zbigniew K
ZK
Uitti
Ryan J
RJ
Nichols
William C
WC
Griffith
Alida
A
Hattori
Nobutaka
N
Leppert
David
D
Watts
Ray
R
Zabetian
Cyrus P
CP
Foroud
Tatiana M
TM
Farrer
Matthew J
MJ
Brice
Alexis
A
Middleton
Lefkos
L
Hentati
Faycal
F
D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics*
D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine