مقاله انگلیسی رایگان در مورد ویژگی های بیماری پارکینسون در حامل های LRRK2 G2019S – الزویر 2018

Introduction: LRRK2 G2019S mutation carriers with Parkinson’s disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is among the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. Methods: This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. Results: We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. Conclusion: Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.

Introduction

The autosomal dominant G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is among the most common genetic mutations associated with PD.[1] This mutation is responsible for 4% of familial PD and 1% of sporadic cases of PD,[2] with a higher frequency of up to 18% of PD in Ashkenazi Jews (and up to 30% of familial cases).[3] The clinical manifestations of PD in LRRK2 mutation carriers were generally similar to those of sporadic PD,[4, 5] although some studies found a milder motor phenotype in carriers.[2, 6] Some authors found that G2019S carriers were more likely to display the postural instability-gait difficulty (PIGD) phenotype with falls.[7, 8] The International LRRK2 Consortium found a higher incidence of tremor as the presenting symptom, prevalence of dystonia, slower motor progression, and lower incidence of cognitive impairment in carriers.[2] Some authors,[9, 10] but not others,[11-14] found less cognitive impairment in G2019S carriers compared to non-carriers with PD. This cross-sectional data collection study sought to compare motor Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and other characteristics between LRRK2 G2019S-positive subjects and matched PD controls without the mutation recruited from an academic medical center in Cleveland, Ohio.