Journal of Molecular Neuroscience

, Volume 44, Issue 1, pp 25–30

Phenotypic Heterogeneity in a SOD1 G93D Italian ALS Family: An Example of Human Model to Study a Complex Disease

  • Silvana Penco
  • Christian Lunetta
  • Lorena Mosca
  • Eleonora Maestri
  • Francesca Avemaria
  • Claudia Tarlarini
  • Maria Cristina Patrosso
  • Alessandro Marocchi
  • Massimo Corbo
Article

DOI: 10.1007/s12031-010-9480-4

Cite this article as:
Penco, S., Lunetta, C., Mosca, L. et al. J Mol Neurosci (2011) 44: 25. doi:10.1007/s12031-010-9480-4

Abstract

We report different clinical expression in seven members of a large family with amyotrophic lateral sclerosis (ALS) and the G93D mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD1) gene. The ALS clinical course in the proband showed an unusually fast progression of the disease compared to the paucisymptomatic presentation associated to this mutation in the two previously Italian families described. The remaining mutation carriers did not show the aggressive clinical course displayed by the proband. We selected few genes known to be ALS modifiers searching for genetic variants that could explain the wide phenotypic diversity within the family. Exclusion of causative genes such as TDP43, FUS, PGRN and VAPB was performed too. We believe that this kind of family with contrasting phenotypes of ALS may be considered an excellent human model to study the relationship between a wider genetic profile, including modifier genes, and the clinical expression of the disease. Therefore, the novelty of our approach is also represented by the study of a single family to reproduce a composite structure in which search for possible modifier genes/genetic variants linked to SOD1 mutated.

Keywords

Complex diseaseFALSGenetic variationsHuman modelSOD1 mutation

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Silvana Penco
    • 1
  • Christian Lunetta
    • 2
  • Lorena Mosca
    • 1
  • Eleonora Maestri
    • 2
  • Francesca Avemaria
    • 1
  • Claudia Tarlarini
    • 1
  • Maria Cristina Patrosso
    • 1
  • Alessandro Marocchi
    • 1
  • Massimo Corbo
    • 2
  1. 1.Department of Laboratory Medicine, Medical GeneticsNiguarda Ca’ Granda HospitalMilanItaly
  2. 2.NEuroMuscular Omnicentre, Fondazione Serena OnlusNiguarda Ca’ Granda HospitalMilanItaly