A comparison of clinical and pathological features of young‐ and old‐onset Parkinson's disease

Gibb, W. R. G.; Lees, A. J.

doi:10.1212/wnl.38.9.1402

Cited by 324 publications

(231 citation statements)

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“…The majority of our study sample consisted of a group of German origin (256 PD patients: 41.6% women; 13 The German controls underwent the same neurological examination as the patients, whereas the Serbian controls had not undergone any clinical examination. Controls were ethnically matched to the patients and comprised 121 populationbased controls collected as part of a study on PD, 41 unaffected spouses of PD patients, and 156 anonymous blood donors.…”

Section: Patientsmentioning

confidence: 99%

Role of ethnicity on the association of MAPT H1 haplotypes and subhaplotypes in Parkinson's disease

et al. 2007

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An association of the H1 haplotype and subhaplotypes in the microtubule-associated protein Tau (MAPT) gene with Parkinson's disease (PD) has been reported. To further evaluate their role in PD, we genotyped a sample set of 765 cases and controls consisting of two large European subgroups of German (n ¼ 418) and Serbian (n ¼ 347) origin for the MAPT haplotypes H1 and H2. The H1/H1 carriers were tested for three additional MAPT polymorphisms. In the Serbian sample, there was significant evidence (P ¼ 0.0108) of an association of the H1/H1 genotype and PD. Surprisingly, in the German sample, we did not find significant differences in genotype or haplotype frequencies between patients and controls. These results suggest that the role of H1 haplotypes in the etiology of PD may be ethnically dependent. IntroductionAlthough in the past decade several monogenic forms of Parkinson's disease (PD) have been identified, the cause of the disease in the majority of cases remains unknown, and a combination of (multiple) susceptibility genes and environmental factors is discussed. 1 Many association studies of various polymorphisms within different candidate genes have been described, often yielding conflicting results and thus precluding definite conclusions.A specific haplotype of the microtubule-associated protein Tau (MAPT) gene, denominated the H1 haplotype, has consistently been reported to be overrepresented in patients with progressive supranuclear palsy, a form of atypical parkinsonism. 2 Furthermore, an association with the H1 haplotype and idiopathic PD has also been demonstrated in most but not all studies. 3 -10 Interestingly, a biological effect of this haplotype was shown in two different cell lines in vitro; the H1 haplotype was more efficient at driving gene expression than the H2 haplotype, suggesting increased MAPT expression as the H1-mediated susceptibility factor in idiopathic PD. 6 Recently, the H1 haplotype of the MAPT gene has been partitioned into several H1-specific subhaplotypes, six of which were exclusively found in Norwegian PD patients, but not in matched controls. 11 The frequency of H1 subhaplotypes tagged with the specific single-nucleotide polymorphism (SNP) markers rs242562 (G/A), rs3785883 (G/A), rs2435207 (G/A) (corresponding to SNPs 1, 13, and 2 in Skipper et al 11 (Figure 1)) was strikingly different between the 81 studied cases and 81 controls. Especially the 'A-A' haplotype, denoted by H1-SNPs 1 and 2, was the most significantly associated one with the disease. Linkage disequilibrium (LD) among these SNPs was significant in cases but not in controls. 11 However, these findings seem to differ between ethnic groups. In a study of 133 Greek patients, the at-risk subhaplotype was the 'G-A' haplotype, represented by the same SNPs. 12 Here, we tested a larger sample set of PD patients and matched controls from two different European populations for an association with the H1 haplotype and these specific SNP markers. The German subgroup represents a Northern European population and should be...

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Section: Patientsmentioning

confidence: 99%

Role of ethnicity on the association of MAPT H1 haplotypes and subhaplotypes in Parkinson's disease

et al. 2007

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“…The diagnosis of PD was based on the UK Brain Bank diagnostic criteria (with the exception that positive family history was not regarded an exclusion criterion). 20 6 In all, 100 chromosomes of Italian and 100 chromosomes of German control individuals were screened for the presence of the novel mutations and the novel polymorphism. The mean age of the controls at the time of the blood collection was 52.2714.3 years.…”

Section: Patientsmentioning

confidence: 99%

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

et al. 2005

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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: 43.275.4 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: 38.279.7 (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.836G4A), and two patients had known Parkin mutations (heterozygous c.734A4T and c.924C4T; heterozygous c.924C4T). Family history was negative for all mutation carriers, but one with a history of tremor. Additionally, we detected one novel polymorphism (c.344A4T) and four novel PINK1 changes of unknown pathogenic significance (À21G/A; IVS1 þ 97A/G; IVS3 þ 38_40delTTT; c.852C4T), 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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“…It is one of the most common progressive neurodegenerative illnesses [1][2][3]. PD diagnosis is clinical, based on these signs: tremor, rigidity, bradykinesia, akinesia or hypokinesia [4,5]. Accurate assessment of patient's complaints, history and clinical examination data is necessary determining PD diagnosis [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Parkinson’s disease: the most common diagnostic mistakes in Lithuania

et al. 2009

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AbstractParkinson’s disease (PD) belongs to group of neurodegenerative diseases. PD diagnosis is clinical, based on these signs: tremor, rigidity, bradykinesia, akinesia or hypokinesia. The aim of the work was to determine the frequency of separate clinical forms of Parkinson’s disease and difficulties at this disease diagnosis. After examining 267 patients, foreseen clinical criterion of Parkinson’s disease correspond 202 (44.0% persons) − 115 women and 87 men and for 65 patients diagnosis of PD was not confirmed, because they did not correspond with accepted criteria of Parkinson’s disease. While analyzing clinical peculiarities of disease we ascertained that rigidity-tremor form of disease prevailed for 152 (75.2%, 86 women and 66 men) patients. The rigidity form was more rare − 28 (13.9%, 13 women and 15 men). Not very frequent was a tremor form of disease -− 22 (10.9%, 16 women and 6 men) patients. According to data of our research, for almost one fourth of patients (65, 24.3%) the diagnosis of Parkinson’s disease was not confirmed after clinical examination. These patients did not correspond with clinical criteria of PD. The data of our research maintain that for almost one fourth (one fourth of what?) (24.3%) the diagnosis was incorrect. Although these patients did not correspond with accepted criteria of PD, they had been treated with antiparkinsonic medications. The PD diagnosis for them was determined only according to separate symptoms: tremor, gait alterations or memory deterioration and behaviour alternations. It must be noted, that symptoms of Wilson’s disease, MSA or brain infarction were estimated as PD. Examining patients at home, we ascertained that not all patients use prescribed L-dopa preparations. A part of patients or their relatives stopped using of this drug independently. We also made note of the fact that urinary incontinence manifested using dopamine agonist ropinirole. This side effect became significant problem for patient himself and for his relatives.

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A comparison of clinical and pathological features of young‐ and old‐onset Parkinson's disease

Cited by 324 publications

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Role of ethnicity on the association of MAPT H1 haplotypes and subhaplotypes in Parkinson's disease

Role of ethnicity on the association of MAPT H1 haplotypes and subhaplotypes in Parkinson's disease

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

Parkinson’s disease: the most common diagnostic mistakes in Lithuania

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