AUTHOR=Vinagre-Aragón Ana , Campo-Caballero David , Mondragón-Rezola Elisabet , Pardina-Vilella Lara , Hernandez Eguiazu Haizea , Gorostidi Ana , Croitoru Ioana , Bergareche Alberto , Ruiz-Martinez Javier 

TITLE=A More Homogeneous Phenotype in Parkinson's Disease Related to R1441G Mutation in the LRRK2 Gene

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.635396

DOI=10.3389/fneur.2021.635396

ISSN=1664-2295

ABSTRACT=Parkinson’s disease (PD) is characterized by a great clinical heterogeneity. Nevertheless, the 
biological drivers of this heterogeneity have not been completely elucidated and are likely to be  complex, arising from interactions between genetic, epigenetic and environmental factors. Despite 
this heterogeneity, the clinical patterns of monogenic forms of PD have usually maintained a good 
clinical correlation with each mutation once a sufficient number of patients have been studied. 
Mutations in LRRK2 are the most commonly known genetic cause of autosomal dominant PD known 
to date. Furthermore, recent genome-wide association studies have revealed variations in LRRK2 as 
significant risk factors also for the development of sporadic PD. The LRRK2-R1441 mutation is 
especially frequent in population of Basque ascent based on a possible founder effect, being 
responsible for almost 50% of cases of familial PD in our region, with a high penetrance. Curiously, 
Lewy bodies, considered the neuropathological hallmark of PD, are absent in a significant subset of 
LRRK2-PD cases (including the neuropathological study of three PD LRRK2-R1441). Indeed, these 
cases appear to be associated with a less aggressive primarily pure motor phenotype. The aim of our 
research is to examine the clinical phenotype of R1441G-PD patients, more homogeneous when we 
compare it with idiopathic PD patients or with patients carrying other LRRK2 mutations, and reflect 
on the value of the observed correlation in the genetic forms of PD. The clinical heterogeneity of PD 
leads us to think that there may be as many different diseases as the number of people affected. 
Undoubtedly, genetics constitutes a relevant key player, as it may significantly influence the 
phenotype, with differences according to the mutation within in the same gene, and not only in 
familial PD but also in sporadic forms. Thus, extending our knowledge regarding genetic forms of 
PD implies an expansion of knowledge regarding sporadic forms and this may be relevant due to the 
future therapeutic implications of all forms of PD.