Prevalence and Phenotypic Spectrum of PINK1 Mutations in Parkinson’s Disease

Abstract

Several genes have been identified as causative of autosomal dominant or recessive forms of Parkinson’s disease (PD). Bi-allelic mutations in the PTEN-induced putative kinase 1 ( PINK1 ) gene represent the second most frequent cause of autosomal recessive parkinsonism (ARP) after PARK2/ Parkin . The typical PINK1 -associated phenotype is characterized by early age at onset, slow disease progression, and excellent and sustained response to levodopa, but in rare cases the clinical presentation can be indistinguishable from that of sporadic PD. Single heterozygous rare variants in the PINK1 gene, as well as in other ARP genes, have been frequently detected both in parkinsonian patients and in healthy controls. Although their pathogenetic role is still debated, these variants have been suggested to act as minor risk factors for developing PD.