A novel SPAST gene splicing variant (c.1617-2A>C) in a heterozygous carrier with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of lower limbs. We report a novel splicing variant (c.1617-2A>C) of the SPAST gene in a heterozygous carrier from an Italian family with autosomal dominant HSP. The case study describes a pure form of spastic paraparesis with the cardinal clinical features of SPG4. The novel variant affects a canonical splice site and is likely to disrupt RNA splicing. We conclude that the c.1617-2A>C substitution is a null variant, which could be classified as pathogenic; its penetrance should be further investigated. •Hereditary spastic paraplegia (HSP) denotes a group of clinically and genetically heterogeneous neurodegenerative disorders; the identification of the underlying pathogenic variant is crucial.•The case study presents a 59-years-old woman with progressive spasticity and weakness of lower limbs; family history was suggestive for HSP.•Genetic analysis demonstrated a novel heterozygous variant (c.1617-2A>C) of the SPAST gene, which was predicted to disrupt RNA splicing.•Based on clinical and molecular findings, the c.1617-2A>C substitution could be classified as a pathogenic null variant associated with SPG4.