Novel mutation of

Area of Science:

• Neurogenetics
• Molecular Biology
• Clinical Neurology

Background:

• Hereditary spastic paraplegia (HSP) comprises neurogenetic disorders affecting the corticospinal tract, characterized by lower limb spasticity and weakness.
• Mutations in the spastic paraplegia type 4 (SPG4) gene, encoding spastin, are a primary cause of HSP.
• This research focuses on a Chinese family presenting with HSP due to a novel SPG4 gene mutation.

Observation:

• A 44-year-old male presented with progressive lower limb weakness, stiffness, and gait instability, without significant muscle atrophy.
• Neurological exams indicated normal lower limb muscle strength but hyperreflexia and positive Babinski signs.
• Similar symptoms were reported in other family members, suggesting a hereditary pattern.

Findings:

• Mutation analysis revealed a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), in the SPG4 gene within the affected family.
• This mutation was identified as the cause of autosomal dominant, pure hereditary spastic paraplegia in the family.
• Clinical data, including age of onset and sex distribution, were analyzed for all affected family members.

Implications:

• The discovery of this novel SPG4 mutation broadens the understanding of genetic variations leading to hereditary spastic paraplegia.
• This case contributes to the growing knowledge base of SPG4 gene mutations and their clinical impact.
• Further research into this mutation may offer insights into the pathogenesis and potential therapeutic targets for SPG4-related HSP.