Possible Anticipation in Hereditary Spastic Paraplegia Type 4 (SPG4) | Canadian Journal of Neurological Sciences | Cambridge Core (original) (raw)

Article contents

Abstract

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Objective:

We report a multigenerational family with uncomplicated hereditary spastic paraplegia type 4 and apparent anticipation. Genetic analysis of the proband revealed a frame shift mutation (5 base pair deletion) in exon 9 of the SPG4 gene encoding the spastin protein. We hypothesized that this deletion mutation may be dynamic and variability in the size of the deletion could account for the anticipation.

Methods:

Clinical and genetic analysis of this family and the deletion mutation.

Results:

In this family, the age of onset, which ranges from 3 to 50 years shows an average decrease in the age of onset of 21.8 years per transmission over three generations. Genetic analysis of multiple family members indicates that all affected members carry the same c.1340_1344deITATAA mutation and that it is not dynamic.

Conclusion:

In this family, other molecular mechanisms may contribute to development of anticipation.

Résumé:

RÉSUMÉ:Objectif :

Nous rapportons le cas d'une famille de plusieurs générations atteinte de paraplégie spastique héréditaire (PSH) de type 4 non compliquée et ce qui semble être un phénomène d'anticipation. L'analyse génétique chez le cas index a montré une mutation à trame décalée (délétion de 5 paires de bases) dans l'exon 9 du gène SPG4 qui code la synthèse de la spastine. Nous avons émis l'hypothèse que cette délétion puisse être dynamique et que la variabilité de la taille de la délétion puisse être responsable d'un phénomène d'anticipation.

Méthodes :

Analyse clinique et génétique de cette famille et de sa mutation.

Résultats :

Dans cette famille, on note une diminution moyenne de 21,8 ans par transmission sur trois générations, l'âge de début variant de 3 à 50 ans. L'analyse génétique effectuée chez plusieurs membres de la famille indique que tous les individus atteints sont porteurs de la même mutation c.1340_1344delTATAA qui n'est pas dynamique.

Conclusion :

Il est possible qu'un autre mécanisme moléculaire contribue à l'anticipation observée dans cette famille.

Type

Original Articles

Copyright

Copyright © The Canadian Journal of Neurological 2007

References

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