Novel SPAST Deletion Mutation in an American Family With Hereditary Spastic Paraplegia: A Case Report.

The diverse group of neurodegenerative disorders known as hereditary spastic paraplegia (HSP) is characterized by spasticity and weakness of the bilateral lower extremity due to degeneration of the corticospinal tract. The pathogenesis of HSP is broad, with autosomal dominant, autosomal recessive, X-linked recessive, mitochondrial inheritance, and de novo mutations reported, along with remarkable heterogeneity of mutations and clinical presentation. Of these, the most common subtype of HSP is HSP type 4 (HSP-SPG4), a result of mutations in the SPAST gene (chromosome 2p22.3) that leads to impaired activity of the microtubule-severing protein spastin. Typically presenting as an uncomplicated, autosomal dominant form of the disease, HSP-SPG4 has been documented worldwide with vast genomic variance across the SPAST gene. Despite common features in clinical phenotypes, a clear link between SPAST gene variants and disease presentation remains vague. Here, we report a novel 26.1 kb deletion in the SPAST gene (del exons 4-7) in a US family with previously undiagnosed HSP-SPG4.