title: PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism.
abstract: Recessively inherited early-onset parkinsonism (EOP) has been associated with mutations in the Parkin, DJ-1, and PINK1 genes. We studied the prevalence of mutations in all three genes in 65 Italian patients (mean age of onset: 43.2+/-5.4 years, 62 sporadic, three familial), selected by age at onset equal or younger than 51 years. Clinical features were compatible with idiopathic Parkinson's disease in all cases. To detect small sequence alterations in Parkin, DJ-1, and PINK1, we performed a conventional mutational analysis (SSCP/dHPLC/sequencing) of all coding exons of these genes. To test for the presence of exon rearrangements in PINK1, we established a new quantitative duplex PCR assay. Gene dosage alterations in Parkin and DJ-1 were excluded using previously reported protocols. Five patients (8%; one woman/four men; mean age at onset: 38.2+/-9.7 (range 25-49) years) carried mutations in one of the genes studied: three cases had novel PINK1 mutations, one of which occurred twice (homozygous c.1602_1603insCAA; heterozygous c.1602_1603insCAA; heterozygous c.836G>A), and two patients had known Parkin mutations (heterozygous c.734A>T and c.924C>T; heterozygous c.924C>T). Family history was negative for all mutation carriers, but one with a history of tremor. Additionally, we detected one novel polymorphism (c.344A>T) and four novel PINK1 changes of unknown pathogenic significance (-21G/A; IVS1+97A/G; IVS3+38_40delTTT; c.852C>T), but no exon rearrangements. No mutations were found in the DJ-1 gene. The number of mutation carriers in both the Parkin and the PINK1 gene in our cohort is low but comparable, suggesting that PINK1 has to be considered in EOP.
authors.affiliation: Department of Neurology, University of Lübeck, Lübeck, Germany. christine.klein@neuro.uni-luebeck.de
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Katja
authors.initials: K
authors.lastname: Hedrich
authors.forename: Nora
authors.initials: N
authors.lastname: Schäfer
authors.forename: Cesa
authors.initials: C
authors.lastname: Scaglione
authors.forename: Roberta
authors.initials: R
authors.lastname: Marchese
authors.forename: Norman
authors.initials: N
authors.lastname: Kock
authors.forename: Birgitt
authors.initials: B
authors.lastname: Schüle
authors.forename: Anja
authors.initials: A
authors.lastname: Hiller
authors.forename: Thora
authors.initials: T
authors.lastname: Lohnau
authors.forename: Susen
authors.initials: S
authors.lastname: Winkler
authors.forename: Karin
authors.initials: K
authors.lastname: Wiegers
authors.forename: Robert
authors.initials: R
authors.lastname: Hering
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abbruzzese
authors.forename: Paolo
authors.initials: P
authors.lastname: Martinelli
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D017384:Sequence Deletion