PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset Parkinsonism

Department of Neurology, University of Lübeck, Lübeck, Germany.
European Journal of HumanGenetics (Impact Factor: 4.35). 10/2005; 13(9):1086-93. DOI: 10.1038/sj.ejhg.5201455
Source: PubMed


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.

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Available from: Birgitt Schuele, Aug 12, 2014
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    • "Mutations in the PINK1 gene on chromosome 1p36 have been reported in ~5% of patients with autosomal recessive PD (13). PINK1 mutations have been reported in patients with autosomal recessive early-onset PD (AREP) in Italy (14,15). The frequency of PINK1 mutations in patients with AREP is between 2.9 and 29%, with the mutation frequency varying greatly depending on ethnicity (16–20). "
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    • "After the identification of the PARK6 locus in 2001, two point mutations have been reported in the PINK1 gene: G309D in a Spanish family and W437X in two Italian families (Valente et al., 2001, 2004a). Several studies have then described various point mutations and more rarely exon deletions (Hatano et al., 2004; Healy et al., 2004; Rogaeva et al., 2004; Valente et al., 2004b; Bonifati et al., 2005; Klein et al., 2005; Li et al., 2005; Ibanez et al., 2006). PINK1 has an intermediate frequency between Parkin and DJ1, estimated as 1%–9% with a great variability being present among different ethnicities (Thomas and Beal, 2007). "
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