Clinical feature and alpha-synuclein level of restless legs syndrome with leucine-rich repeat kinase 2 encoding gene mutation.

INTRODUCTION: Restless leg syndrome (RLS) has been reported associated with Parkinson's Disease (PD). However, it remained largely unknown of the mechanism underlying this association between RLS and PD. METHODS: 199 idiopathic RLS and 114 PD were diagnosed and recruited by neurologists from Ruijin Hospital affiliated to Shanghai Jiao Tong University. And 273 health controls were recruited from community. Eight LRRK2 pathogenic variants were sequenced. Clinical data was collected including symptoms, comorbidities, family history, and iron level. ELISA was used to measure plasma level of α-synuclein. RESULTS: The G2385R variant was found significantly higher in PD group after Bonferroni correction (p = 0.018). Taking all LRRK2 mutations as one risk covariant, further logistic regression analysis showed a marginal association of LRRK2 with RLS (OR = 1.847, 95 %CI:1.022-3.337, p = 0.042) after adjusting age and gender. In terms of clinical feature, it was found that RLS-LRRK2 carriers usually reported a positive family history of neurological or psychiatric disorders including PD, RLS, dementia and depression (48.3 % vs 27.6 %)(p = 0.026) and a higher foot involvement of sensory symptoms (33.3 % vs 14.0 %)(p = 0.042). Plasma α-synuclein level in RLS (p = 0.021) and PD (p = 0.018) was both significantly increased compared to non-manifesting carriers. CONCLUSION: Our study showed that LRRK2 mutation was associated with Chinese PD patients but only showed a possible trend of association with RLS. Positive neurological or psychiatric family history and foot discomfort in RLS were important features of indication of LRRK2 mutation in RLS. Plasma α-syn was increased in LRRK2-RLS as well as LRRK2-PD, indicating a possible association of RLS with PD in LRRK2 carriers.