A novel missense mutation in SPAST causes hereditary spastic paraplegia in male members of a family: A case report

Hereditary spastic paraplegia (HSP) comprises a group of hereditary and neurodegenerative diseases that are characterized by axonal degeneration or demyelination of bilateral corticospinal tracts in the spinal cord; affected patients exhibit progressive spasticity and weakness in the lower limbs. The most common manifestation of HSP is spastic paraplegia type 4 (SPG4), which is caused by mutations in the spastin (SPAST) gene. The present study reports the clinical characteristics of affected individuals and sequencing analysis of a mutation that caused SPG4 in a family. All affected family members exhibited spasticity and weakness of the lower limbs and, notably, only male members of the family were affected. Whole-exome sequencing revealed that all affected individuals had a novel c.1785C>A (p. Ser595Arg) missense mutation in SPAST. Bioinformatics analysis revealed changes in both secondary and tertiary structures of the mutated protein. The novel missense mutation in SPAST supported the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations that cause SPG4. Analysis of SPAST sequences revealed that most pathogenic mutations occurred in the AAA domain of the protein, which may have a close relationship with SPG4 pathogenesis.

Automated summary

This study reports a mutation causing SPG4 and describes the clinical characteristics of affected family members. All affected individuals in the family exhibited lower limb spasticity and weakness, and only males were affected. Whole-exome sequencing revealed a novel c.1785C>A (p. Ser595Arg) missense mutation in the SPAST gene in all affected individuals. Bioinformatics analysis showed changes in the secondary and tertiary structures of the mutated protein. This novel missense mutation in SPAST supports the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations causing SPG4.