AUTHOR=Guadagnolo Daniele , Piane Maria , Torrisi Maria Rosaria , Pizzuti Antonio , Petrucci Simona 

TITLE=Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.648588

DOI=10.3389/fneur.2021.648588

ISSN=1664-2295

ABSTRACT=Parkinson Disease (PD) is a complex neurodegenerative disorder, characterized by prominent movement disorders and non-motor symptoms. usually with multifactorial etiology. A fraction of PD cases is due instead to Parkinsonian conditions with Mendelian inheritance. The study of the genetic causes of these phenotypes has shed light onto common pathogenetic mechanisms underlying Parkinsonian conditions. Monogenic Parkinsonisms can present autosomal dominant, autosomal recessive or even X-linked inheritance pattern. Clinical presentations vary from forms indistinguishable from idiopathic PD to severe childhood onset conditions with other neurological signs. We provided a comprehensive description of each condition, discussing current knowledge on genotype-phenotype correlations. Despite the broad clinical spectrum and the many genes involved, the phenotype appears to be related to the disrupted cell function and inheritance pattern, and several assumptions about genotype-phenotypes correlations can be made. The interest in these assumptions is not merely speculative, in the light of novel promising target therapies currently under development.