LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic.

Abstract:

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.

journal_name

Acta Neurol Scand

authors

Ben Romdhan S,Farhat N,Nasri A,Lesage S,Hdiji O,Ben Djebara M,Landoulsi Z,Stevanin G,Brice A,Damak M,Gouider R,Mhiri C

doi

10.1111/ane.12996

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

425-431

issue

5

eissn

0001-6314

issn

1600-0404

journal_volume

138

pub_type

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