title: Late onset sporadic Parkinson's disease caused by PINK1 mutations: clinical and functional study.
abstract: Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin. The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease progression, and better response to therapy. Indeed, the rare patients with onset above 50 years are usually relatives of early-onset probands. Here, we report the first occurrence of compound heterozygous PINK1 mutations in a sporadic patient with a phenotype indistinguishable from idiopathic Parkinson's disease (PD), with onset in the late seventh decade, rapid progression and good response to levodopa that waned with time. Both mutations (p.A244G and p.V317I) were found to abolish the protective effect of wild-type PINK1 against staurosporine-induced apoptosis. These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD.
authors.affiliation: IRCCS CSS-Mendel Institute, Rome, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Gelmetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Livia
authors.initials: L
authors.lastname: Brusa
authors.forename: Francesca
authors.initials: F
authors.lastname: Romano
authors.forename: Federica
authors.initials: F
authors.lastname: Lombardi
authors.forename: Chiara
authors.initials: C
authors.lastname: Barzaghi
authors.forename: Paolo
authors.initials: P
authors.lastname: Stanzione
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D019311:Staurosporine; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein