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SPG4 Founder Effect in French Canadians with Hereditary Spastic Paraplegia

Published online by Cambridge University Press:  02 December 2014

Inge A. Meijer ,
Nicolas Dupré ,
Bernard Brais ,
Patrick Cossette ,
Judith St-Onge ,
Marie-France Rioux ,
Melanie Benard  and
Guy A. Rouleau
Inge A. Meijer
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
Nicolas Dupré
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
Bernard Brais
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
Patrick Cossette
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
Marie-France Rioux
Affiliation:
Service de neurologic, Centre hospitalier de l'Université de Sherbrooke, Sherbrooke, QC, Canada
Melanie Benard
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
Guy A. Rouleau
Affiliation:
Center for the Study of Brain Diseases, CHUM Research Center, Notre-Dame Hospital
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Abstract

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Background:

The most common cause of autosomal dominant Hereditary Spastic Paraplegia (HSP) is mutations in the SPG4 gene. We have previously identified novel SPG4 mutations in a collection of North American families including the c.G1801A mutation present in two families from Quebec. The aim of this study is to estimate the frequency of the c.G1801A mutation in the French Canadian (FC) population and to determine whether this mutation originates from a common ancestor.

Methods:

We collected and sequenced exon 15 in probands of 37 families. Genotypes of markers flanking the SPG4 gene were used to construct haplotypes in five families. Clinical information was reviewed by a neurologist with expertise in HSP.

Results:

We have identified three additional unrelated families with the c.G1801A mutation and haplotype analysis revealed that all five families share a common ancestor. The mutation is present in 7% of all our FC families and explains half of our spastin linked FC families. The phenotype associated with the c.G1801A genotype is pure HSP with bladder involvement.

Conclusion:

In this study we have determined that the relative frequency of the c.G1801A mutation in our FC collection is 7%, and approximately 50% in the spastin positive FC group. This mutation is the most common HSP mutation identified in this population to date and is suggestive of a founder effect in Quebec.

Résumé:

RÉSUMÉ:Contexte:

La cause la plus fréquente de la paraplégie spastique héréditaire (PSH) dominante autosomique est une mutation du gène SPG4. Nous avons déjà identifié de nouvelles mutations du gène SPG4 dans un groupe de familles nord-américaines, dont la mutation c.G1801A qui est présente chez 2 familles du Québec. Le but de cette étude était d'estimer la fréquence de la mutation c.G1801A dans la population canadienne-française (CF) et de déterminer si cette mutation provient d'un ancêtre commun.

Méthodes :

Nous avons recueilli et séquencé l'exon 15 de chacun des cas index des 37 familles. Le génotypage de marqueurs adjacents au gène SPG4 a été utilisé pour construire des haplotypes dans 5 familles. Les données cliniques ont été révisées par un neurologue ayant une expertise dans le domaine de la PSH.

Résultats :

Nous avons identifié 3 autres familles non apparentées qui ont la mutation c.G1801A et l'analyse des haplotypes a montré que ces 5 familles ont un ancêtre commun. La mutation est présente chez 7% de nos familles CF et explique la maladie liée à la spastine chez la moitié de nos familles CF. Le phénotype associé au génotype cG1801A est une PSH pure avec atteinte vésicale.

Conclusion:

Nous avons établi que la fréquence relative de la mutation cG1801A chez nos cas CF est de 7% et de 50% dans le groupe de cas CF positifs pour la spastine. C'est la mutation la plus fréquente dans le gène de la PSH qui ait été identifiée dans cette population jusqu'à maintenant et nos données sont compatibles avec la présence d'un effet fondateur au Québec.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 2 , May 2007 , pp. 211 - 214
Copyright
Copyright © The Canadian Journal of Neurological 2007

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