The clinical picture of all patients with the LRRK2-G2019S mutation was typical for levodopa-responsive parkinsonism and age of disease onset varied widely (from 39 to 71 years).
Mutations in five causative genes combined [alpha-Synuclein (SNCA), Parkin, PTEN-induced kinase 1 (PINK1), DJ-1, Leucine-rich repeat kinase 2 (LRRK2)] account for 2-3% of all cases with classical parkinsonism, often clinically indistinguishable from idiopathic Parkinson's disease.
Since the discovery in 1997 of the first heritable form of parkinsonism that could be linked to a mutation in a single gene, SNCA, many more genetic leads have followed (Parkin, DJ-1, PINK1, LRRK2, to name a few); these have provided us with many molecular clues to better explore the etiology of parkinsonism and have led to the dismantling of many previously held dogmas about Parkinson disease (PD).
We discuss the roles of heterozygous LRRK2 mutations and heterozygous parkin and PINK1 mutations in the development of parkinsonism, and propose an integrated aetiological model for this complex disease.
However we can not rule out other genetic variation at the LRRK2 locus may play a role in parkinsonian disorders with amyotrophic lateral sclerosis and may be considered candidates for genetic screening.
Leucine-rich repeat kinase 2 (LRRK2) mutation carriers can develop clinical symptoms other than typical parkinsonism such as dementia, amyotrophy or dystonia.
The localization of LRRK2 to key neuronal populations throughout the nigrostriatal dopaminergic pathway is consistent with the involvement of LRRK2 in the molecular pathogenesis of familial and sporadic parkinsonism.
The leucine-rich repeat kinase 2 (Lrrk2) G2385R substitution is associated with familial parkinsonism, late-, and early-onset Parkinson's disease in ethnic Chinese Taiwanese.
Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism.
Our findings highlight the importance of Lrrk2parkinsonism in this population and may have important consequences for its extended Diaspora in North, Central and South Americas.
In this brain bank-based series, LRRK2G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as a much more common cause for dominant PS, especially in certain ethnic groups, while mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 cause autosomal recessive parkinsonism of early onset.
In this brain bank-based series, LRRK2 G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration.
We conducted PET of 2 subjects and neuropathologically examined 8 subjects in the same family from the Sagamihara district, the original source of PARK8-linked parkinsonism (I2020T mutation).