PDF(Pubmed)
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.
摘要：
4型痉挛性截瘫(SPG4),常染色体显性遗传性痉挛性截瘫（AD-HSP）的主要形式，其特征在于SPAST基因中的变体。这项研究报告了一个独特的病例，在一名汉族男性中晚发性SPG4，主要表现为下肢痉挛引起的步态障碍。通过全基因组测序发现，以前没有记录的移码变体，在SPAST基因的第14外显子c.1545dupA，已确定。值得注意的是,在确认父亲和母亲身份的无症状父母中不存在这种变异，提示从头变异的发生。这一发现强调了从头变体表现出迟发性纯模式的潜力，扩展SPG4变异谱，在家族史阴性的HSP患者中应考虑此类变异。
