Neurogenetics

, Volume 8, Issue 3, pp 231–233

A de novo SPAST mutation leading to somatic mosaicism is associated with a later age at onset in HSP

Authors

  • Christel Depienne
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
    • Département de GénétiqueCytogénétique et Embryologie
    • Université Pierre et Marie Curie
  • Estelle Fedirko
    • Département de GénétiqueCytogénétique et Embryologie
  • Jean-Marc Faucheux
    • Centre hospitalier
  • Sylvie Forlani
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
  • Bernard Bricka
    • Département de GénétiqueCytogénétique et Embryologie
  • Cyril Goizet
    • Hôpital Pellegrin
  • Sylvie Lesourd
    • Département de GénétiqueCytogénétique et Embryologie
    • Université Pierre et Marie Curie
  • Giovanni Stevanin
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
    • Département de GénétiqueCytogénétique et Embryologie
    • Université Pierre et Marie Curie
  • Merle Ruberg
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
  • Alexandra Durr
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
    • Département de GénétiqueCytogénétique et Embryologie
    • INSERM, UMR 679 (formerly U289), GH Pitié-Salpêtrière
    • Département de GénétiqueCytogénétique et Embryologie
    • Université Pierre et Marie Curie
Letter to the Editors

DOI: 10.1007/s10048-007-0090-4

Cite this article as:
Depienne, C., Fedirko, E., Faucheux, J. et al. Neurogenetics (2007) 8: 231. doi:10.1007/s10048-007-0090-4

Abstract

SPG4/SPAST, the gene-encoding spastin, is responsible for the most frequent form of autosomal dominant hereditary spastic paraplegia (HSP). SPG4-HSP is a heterogeneous disorder characterized by both interfamilial and intrafamilial variation, especially regarding the severity and the age at onset. In this study, we investigated the origin of the mutation and the factors involved in intra-familial heterogeneity in a family with a SPG4 mutation. We demonstrated that the mutation occurred de novo and show evidence of somatic mosaicism in the grandfather, who was the only affected member of six siblings. His disease began at age 55, much later than in his daughter, who had onset at age 18, and his grandson, in whom onset was at age 5. These observations indicate that de novo mutations can occur in SPG4, and that somatic mosaicism might account for intra-familial variation in SPG4-linked HSP.

Copyright information

© Springer-Verlag 2007