Hereditary spastic paraplegias (HSPs) are modified by the underlying SPAST mutation and sex

Takeaway 

  • The sex of patients, and the nature of underlying SPAST mutation modify age of onset and severity of hereditary spastic paraplegias (HSPs).

Why this matters

    Spastic paraplegia gene-4 (SPG4) is the most common cause of HSP. Many of these patients with underlying SPAST mutations are asymptomatic, with extreme variability in age of onset and severity. This study correlates age of onset and severity with specific SPAST mutations and identifies novel pathogenic mutations – which could help to characterize disease in asymptomatic patients.