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Familial Parkinson’s Disease: A Clinical Genetic Analysis

Published online by Cambridge University Press:  18 September 2015

Vincenzo Bonifati ,
Edito Fabrizio ,
Nicola Vanacore ,
Michele De Mari  and
Giuseppe Meco
Vincenzo Bonifati*
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Edito Fabrizio
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Nicola Vanacore
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
Michele De Mari
Affiliation:
Institute of Neurology, University of Bari, Italy
Giuseppe Meco
Affiliation:
Department of Neurosciences, “La Sapienza” University, Rome
*
Department of Neurosciences, Viale dell’Università30, 00185 Roma, Italy
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Abstract

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Objective

To study the frequency, clinical features and clinical genetics of familial Parkinson’s disease (PD).

Methods

Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were compared between personally verified familial and sporadic PD cases, from the same consecutive clinical series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families.

Results

Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse controls (p < 0.001). When family history for isolated tremor is also considered, the number of positive cases rises to 43% compared with 9% in controls (p < 0.001). Nine of the consecutive cases had at least one living affected relative, for a total of 20 familial PD cases. These familial cases showed an earlier onset age when compared with sporadic ones from the same consecutive series. Within 22 non-consecutive PD families with at least two living and personally examined PD cases (total 52 PD cases), the crude segregation ratios were similar for parents and siblings and the lifetime cumulative risks approached 0.4 in siblings and tended to be comparable, but at later ages, in parents. Ancestral relatives were all unilaterally distributed. In some families, anticipation of onset age in new generations was observed.

Conclusions

The frequency of positive family history for PD and for PD and tremor is higher among PD cases than controls. Familial and sporadic PD only differ in onset age. The clinical genetic analyses support autosomal dominant inheritance with strongly age-related penetrance as most likely in familial PD.

Résumé

Résumé<span class='italic'><span class='bold'>Objectif</span></span>

Étudier la fréquence, les manifestations cliniques et la génétique clinique de la maladie de Parkinson familiale (MP).

<span class='italic'><span class='bold'>Méthodes</span></span>

Nous avons étudié l’histoire familiale quant à la MP et au tremblement chez 100 cas consécutifs de MP. Les conjoints ont servi de contrôles. Nous avons comparé les manifestations cliniques entre les cas familiaux et sporadiques de MP confirmés personnellement, dans cette même série de cas. Nous avons procédé à une analyse génétique clinique chez un groupe plus considérable de familles comprenant plusieurs cas de MP non consécutifs.

<span class='italic'><span class='bold'>Résultats</span></span>

L’histoire familiale était positive chez 24% des cas consécutifs de MP et chez 6% des conjoints servant de contrôles (p < 0.001). Quand nous tenons également compte d’une histoire familiale de tremblement, le nombre de cas positifs s’élève à 43% comparé à 9% chez les contrôles (p < 0.001). Neuf des cas consécutifs avaient au moins un membre vivant de sa famille qui était atteint, pour un total de 20 cas de MP familiale. Ces cas familiaux présentaient un âge de début plus précoce comparé aux cas sporadiques de la même série de cas consécutifs. Dans 22 familles de MP non consécutives comprenant au moins deux cas de MP vivants et examinés personnellement (pour un total de 52 cas de MP), le ratio de ségrégation brut était le même pour les parents et la fratrie, et le risque cumulatif à vie, qui était de près de 0.4 dans la fratrie, avait tendance à être comparable chez les parents, mais à un âge plus tardif. Les cas dans la parenté plus éloignée étaient toujours dans la même lignée, soit paternelle ou maternelle. Dans certaines familles, nous avons observé un phénomène d’anticipation quant à l’âge de début de la maladie dans les générations subséquentes.

<span class='italic'><span class='bold'>Conclusions</span></span>

Une histoire familiale de MP et de MP et tremblement est plus fréquente parmi les cas de MP que parmi les contrôles. La seule différence entre les cas familiaux et sporadiques est l’âge de début de la maladie. Les analyses génétiques cliniques sont en faveur d’une hérédité autosomale dominante de la MP, avec une penetrance fortement reliée à l’âge.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 22 , Issue 4 , November 1995 , pp. 272 - 279
Copyright
Copyright © Canadian Neurological Sciences Federation 1995

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