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LRRK2 Screening in a Canadian Parkinson's Disease Cohort

Published online by Cambridge University Press:  02 December 2014

D. A. Grimes ,
L. Racacho ,
F. Han ,
M. Panisset  and
D. E. Bulman
D. A. Grimes
Affiliation:
Department of Medicine, Division of Neurology, The Ottawa Hospital Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, ON
L. Racacho
Affiliation:
Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, ON
F. Han
Affiliation:
Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, ON
M. Panisset
Affiliation:
Unité des Troubles du Mouvement André Barbeau, CHUM Hôtel-Dieu, Montreal, QC, Canada
D. E. Bulman
Affiliation:
Department of Medicine, Division of Neurology, The Ottawa Hospital Ottawa Health Research Institute, University of Ottawa, Centre for Neuromuscular Disease, Ottawa, ON
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Abstract

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Background:

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have become the most common known cause for developing Parkinson's disease. The frequency of mutations described in the literature varies widely depending on the population studied with most reports focusing only on screening for the most common G2019S mutation in exon 41.

Methods:

In this study seven exons (19, 24, 25, 31, 35, 38, and 41) in LRRK2 where mutations have been reported were screened in 230 unselected Parkinson's disease patients using denaturing high-performance liquid chromatography.

Results:

The sequencing of samples with heteroduplex profiles revealed five novel and two known intronic sequence variants. In our cohort, we were unable to detect any of the known mutations in these exons or identify novel mutations within the LRRK2 gene.

Conclusions:

Therefore, despite the availability of diagnostic LRRK2 genetic testing it is unlikely to yield a positive result in this population.

Résumé:

RÉSUMÉ:

Dépistage de mutations du gène LRRK2 dans une cohorte de patients canadiens atteints de la maladie de Parkinson.

Contexte:

Les mutations du gène LRRK2 (leucine-rich repeat kinase 2) sont la cause connue la plus fréquente de la maladie de Parkinson (MP). La fréquence des mutations décrites dans la littérature varie beaucoup, selon la population étudiée. La plupart des articles publiés portent seulement sur le dépistage de la mutation la plus fréquente, G2019S, située dans l'exon 41. Méthodes : Nous avons fait le dépistage de mutations dans sept exons (19, 24, 25, 31, 35, 38 et 41) du gène LRRK2 où mutations ont déjà été rapportées, chez 230 patients atteints de la MP choisis au hasard, au moyen de la chromatographie liquide haute performance en conditions dénaturantes. Résultats : Le séquençage des échantillons ayant un profil hétéroduplex a révélé la présence de cinq nouvelles variantes de séquences introniques et de deux connues. Nous n'avons détecté aucune des mutations connues dans ces exons et nous n'avons pas identifié de nouvelles mutations dans le gène LRRK2. Conclusions : Même si un test génétique est disponible pour le gène LRRK2, il est peu probable qu'on obtiendra un résultat positif dans cette population.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 3 , August 2007 , pp. 336 - 338
Copyright
Copyright © The Canadian Journal of Neurological 2007

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