AUTHOR=Xu Yu-Han , Yuan Bao-Yu , Ji Jia-Le , Wu Di , Zhou Hong , Guo Yi-Jing TITLE=Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report JOURNAL=Frontiers in Genetics VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1410381 DOI=10.3389/fgene.2024.1410381 ISSN=1664-8021 ABSTRACT=

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.