LRRK2 G2019S Parkinson’s disease with more benign phenotype than idiopathic.
Acta Neurol Scand. 2018-07-10; 138(5): 425-431
DOI: 10.1111/ane.12996
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1. Acta Neurol Scand. 2018 Nov;138(5):425-431. doi: 10.1111/ane.12996. Epub 2018 Jul
10.
LRRK2 G2019S Parkinson’s disease with more benign phenotype than idiopathic.
Ben Romdhan S(1)(2)(3), Farhat N(1), Nasri A(4), Lesage S(2), Hdiji O(1), Ben
Djebara M(4), Landoulsi Z(4), Stevanin G(2)(3), Brice A(2), Damak M(1), Gouider
R(4), Mhiri C(1).
Author information:
(1)Laboratory of Neurogenetics, Parkinson’s Disease and Cerebrovascular Disease,
University Hospital Habib Bourguiba, Sfax, Tunisia.
(2)Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne
Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France.
(3)École Pratique des Hautes Études EPHE, PSL Research University, Paris, France.
(4)Department of Neurology, University Hospital Razi, Tunis, Mannouba, Tunisia.
OBJECTIVES: The LRRK2-G2019S mutation is the most common cause of Parkinson’s
disease (PD) in North Africa. G2019S-PD has been described as similar to
idiopathic with minor clinical differences. The aim of this study was to
determine the G2019S-related phenotype and to investigate gender and gene dosage
effects on clinical features of G2019S carriers.
PATIENTS AND METHODS: The G2019S mutation was screened in 250 Tunisian patients
with PD. Twenty-four patients carrying mutations in other PD genes were excluded.
Logistic regression models were used to compare clinical features between the
studied groups.
RESULTS: G2019S carriers (107 cases) and non-carriers (119 cases) were similar in
disease duration, levodopa doses, and gender and phenotype distributions.
However, carriers had a younger age at examination, higher level of education,
and were more likely to report family history of PD and to develop PD at earlier
age (P = 0.017). Adjusted for age, sex, disease duration, levodopa-equivalent
dose and educational level, MMSE scores remained significantly higher (adjust
P = 0.019) and UPDRS-III scores were lower (adjust P = 0.012) in the G2019S
carriers than non-carriers. Demographic characteristics of men and women with
G2019S mutation were similar, but men had higher level of education, better
cognition (adjust P-value for educational level = 0.042) and less tendency
towards depression than females (adjust P = 0.046). Furthermore, PD phenotype did
not differ between the homozygous and heterozygous G2019S carriers.
CONCLUSION: In this study, G2019S carriers had a more benign phenotype than
non-carriers. Cognitive impairment and depression were less common in G2019S male
carriers compared with females. In addition, we found that LRRK2 gene dosage does
not influence the severity of PD.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
DOI: 10.1111/ane.12996
PMID: 29989150 [Indexed for MEDLINE]