DJ‐1 gene mutations have been found to cause early‐onset Parkinson's disease. We report a family from southern Italy with three brothers affected by early‐onset parkinsonism, dementia, and ...amyotrophic lateral sclerosis. Molecular analysis of the DJ‐1 gene in two living patients showed a novel homozygous mutation in exon 7 (E163K) and a new homozygous mutation (g.168_185dup) in the promoter region of the gene. Both mutations cosegregated with the disease and were detected in a heterozygous state in the patients' mother and their healthy siblings. Our findings expand the spectrum of clinical presentations associated with mutations in DJ‐1 gene. Ann Neurol 2005;58:803–807
The dopamine D2 receptor (DRD2) gene has been proposed as a candidate gene underlying several psychiatric and neurologic disorders. The aim of the present study was to examine if selected ...polymorphisms in the DRD2 gene are associated with Parkinson's disease (PD). We determined the allelic frequencies for four polymorphisms located in the DRD2 gene in a sample of 135 patients with PD and 202 normal control subjects. No significant difference was observed in the allelic frequencies between patients with PD and control subjects with regard to the ‐141C Ins/Del and the Ser311/Cys311 variants. On the contrary, the A1 allele of the TaqIA polymorphism and the B1 allele of the TaqIB polymorphism were more frequent in patients with PD than in control subjects (control subjects: TaqIA A1 = 14.6%, TaqIB B1 = 10.6%; patients with PD: TaqIA A1 = 20.7%, TaqIB B1 = 17.4%). Patients carrying the A1 allele or the B1 allele had an increased risk of developing PD (TaqIA, odds ratio: 1.71, 95% confidence intervals: 1.08–2.73; TaqIB, odds ratio: 1.83, 95% confidence intervals: 1.12–3.02). The TaqIA and TaqIB polymorphisms were in strong linkage disequilibrium, suggesting that these two polymorphisms convey the same information about the risk of presenting with PD. Genetic variation in the DRD2 gene may influence the risk of developing PD, thus confirming that the DRD2 gene is a susceptibility locus for PD.
Iron overload may lead to neurodegenerative disorders such as Parkinson’s disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of ...haemochromatosis (
HFE)
encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the
HFE
gene, G258S in the
TF
gene and S82G in the
TFR
gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD. No significant differences were found in genotype and allele frequencies between PD and controls for all the polymorphisms studied, suggesting that these variants do not contribute significantly to the risk of PD.
Abstract In this study we analysed the DJ-1 gene in 40 sporadic patients with early onset Parkinson's disease and 100 appropriate controls, originated from southern Italy. We identified a single ...patient with age at onset of 38 years carrying two previously undescribed heterozygous mutations, both located in non-coding regions. The first mutation was a nucleotide change in the promoter region of the gene (g.159 C>G) and the second one was an insertion in the intron 4 splice site (IVS4+3insA). In the same patient, genomic rearrangements were excluded. No DJ-1 mutations were found in the remaining parkinsonian patients. Our results support the growing importance of mutations in non-coding portion of human genome, and confirm that alterations in DJ-1 are a cause, even if rare, of early-onset Parkinson's disease.
Abstract Mutations in the PINK1 gene represent the second most frequent cause of early-onset Parkinson’s disease (EOPD). One or two mutated alleles were also reported in some sporadic or familial ...patients suffering from late-onset Parkinson’s disease (LOPD). We aimed at assessing the frequency of mutations in this gene in our population. We performed a sequence analysis of PINK1 in 115 patients diagnosed with Parkinson’s disease (PD) from southern Italy, including 93 sporadic cases with EOPD, 9 familial cases with EOPD, and 13 familial cases with LOPD. Three known homozygous mutations (Q456X, W437X, Q126P), corresponding to a 2.6% of all cases, were found. In particular, one mutation was detected among the sporadic cases (1.0%), one mutation among the familial early-onset patients (11.1%) and one mutation among the familial late-onset patients (7.7%). In addition, we found two heterozygous mutations (E476K, R207Q) among the sporadic patients. Only one mutation (R207Q) had not been previously described. Our results assess the role played by PINK1 in EOPD in southern Italy and illustrate the existence of mutations in this gene also in the late-onset form of the disease.
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