title: Bridging Over the Troubled Heterogeneity of SPG-Related Pathologies: Mechanisms Unite What Genetics Divide.
abstract: The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms. The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients.
authors.forename: A
authors.initials: A
authors.lastname: Tessa
authors.forename: P S
authors.initials: PS
authors.lastname: Denora
authors.forename: L
authors.initials: L
authors.lastname: Racis
authors.forename: E
authors.initials: E
authors.lastname: Storti
authors.forename: A
authors.initials: A
authors.lastname: Orlacchio
authors.affiliation: Molecular Medicine, IRCCS Fondazione Stella Maris, via dei Giacinti 2, 56128 Calambrone, Pisa, Italy.
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
keywords: Hereditary spastic paraplegia; SPG; genetic; genotype/phenotype correlations; heterogeneity; mechanisms of
  disease; mutation