A clinical genetic study of Parkinson's disease

Lazzarini, Alice; Myers, Richard H.; Zimmerman, Thomas; Mark, Margery H.; Golbe, L. I.; Sage, Jacob I.; Johnson, William G.; Duvoisin, Roger C.

doi:10.1212/wnl.44.3_part_1.499

Cited by 133 publications

(78 citation statements)

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“…This finding is in agreement with previous clinic-based studies (based on family history accounts of patients). 2 ' 7,8 Fourth, the magnitude of increasing risk of PD mirrors that expected on the basis of shared genetic makeup with the proband, that is, first degree relatives have a greater risk than second degree relatives by approximately eight-fold. However, this finding must be considered carefully as other explanations, such as a possible case ascertainment bias favoring first degree relatives, may be important in explaining the disparity in prevalence between first and second degree relatives.…”

Section: Le Journal Canadien Des Sciences Neurologiquesmentioning

confidence: 97%

“Familial Parkinson's Disease” – A Case-Control Study of Families

Uitti

Shinotoh

Hayward

et al. 1997

Can. j. neurol. sci.

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ABSTRACT:Background: Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of "familial PD"(fPD). Methods: 81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined. Results: On examination, 8 persons, said to be "normal" by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100 000 versus 1190/100 000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100 000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree. Conclusions: "Familial parkinsonism" cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a "negative" family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population -regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD. RESUME: "Maladie de Parkinson familiale" -Une etude familiale cas-temoins. Introduction: Les patients atteints de la maladie de Parkinson (MP) rapportent souvent une histoire familiale de MP, ce qui pourrait fournir des indices etiologiques sur la MP. 11 a egalement ete suggere qu'on peut se fier a une histoire familiale negative fournie par le patient. Nous avons etudie la prevalence de la MP chez les apparentes de patients atteints de la MP pour evaluer la fiabilite de l'histoire familiale et identifier des explications possibles dans la "MP familiale". Methodes: 81 des 650 (12.5%) des propositi (tous les patients examines a la clinique en 4 ans) ont rapporte une histoire familiale positive de MP. Chaque cas familial de MP (fMP) a ete apparie pour le sexe et l'annee de naissance a un cas non familial (nfMP). Des questionnaires de depistage et de suivi ont ete postes aux apparentes pour obtenir de l'information concernant l'arbre genealogique et la presence de maladies neurodegenerati...

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Section: Le Journal Canadien Des Sciences Neurologiquesmentioning

confidence: 97%

“Familial Parkinson's Disease” – A Case-Control Study of Families

Uitti

Shinotoh

Hayward

et al. 1997

Can. j. neurol. sci.

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“…Several case-control studies have consistently indicated that PD is more common among relatives of index patients with PD compared with a matched control population, as between 6 and 30 % of index patients had first-or seconddegree affected relatives (Lazzarini et al 1994 ;Payami et al 1994 ;Bonifati et al 1995 ;De Michele et al 1996 ;Marder et al 1996). However, these studies were subject to recall bias.…”

Section: Epidemiological Studiesmentioning

confidence: 99%

Genetics of Parkinsonism: a review

VAUGHAN¹,

DAVIS²,

WOOD³

2001

Annals of Human Genetics

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Idiopathic Parkinson's disease (IPD), a progressive neurodegenerative disorder, is a common cause of disability. No current therapies modify disease progression. The pathological hallmarks are the presence of Lewy bodies and massive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Two genes (SNCA and parkin) as well as two gene loci have now been implicated in the pathogenesis of familial PD. These represent significant progress in our understanding of the disease, considering the rarity of large families, low heritability in the general population and genetic heterogeneity. Mutations in a further gene, UCHL1, have been described in familial PD although the evidence for its role in PD is less clear. Knowledge of the genes described in PD to date should help to define molecular mechanisms of neurodegeneration in PD, as well as in other diseases where defects in protein handling may be a common feature. Nigral degeneration with Lewy body formation and the resulting clinical picture of PD may represent a final common pathway of a multifactorial disease process in which both environmental and genetic factors have a role. This review discusses the major advances in the field to date and illustrates how the existence of genetic factors has now become firmly established.

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“…In many cases a heritable factor predisposes to the development of the clinical syndrome (2). We have recently shown that genetic markers on human chromosome 4q21-q23 segregate with the PD phenotype in a large family of Italian descent (3).…”

mentioning

confidence: 99%

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

Polymeropoulos

Lavedan

Leroy

et al. 1997

Science

7,522

5,036

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Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.

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A clinical genetic study of Parkinson's disease

Cited by 133 publications

References 0 publications

“Familial Parkinson's Disease” – A Case-Control Study of Families

“Familial Parkinson's Disease” – A Case-Control Study of Families

Genetics of Parkinsonism: a review

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

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