Heterozygous mutations in SPTAN1 are associated with a broad phenotypical spectrum ranging from axonal neuropathy phenotypes to neurodevelopmental phenotypes with or without epilepsy. Recently, biallelic mutations in SPTAN1 were reported as a potential cause of autosomal recessive pure hereditary spastic paraplegia (HSP). However, no further HSP cases with biallelic SPTAN1 mutations have been reported. Herein, we report the clinical and genetic findings of a patient with complicated HSP likely caused by a novel homozygous SPTAN1 mutation. A patient with complicated HSP from a consanguineous family was recruited. The proband underwent detailed neurological examinations. Homozygosity mapping was performed in the proband and her healthy sister. Whole exome sequencing was performed in the proband. Our patient had early onset motor symptoms with upper motor neuron paralysis and intellectual disability, which is compatible with complicated HSP. Genetic analysis identified a rare homozygous missense mutation in SPTAN1 (c.4162A>G, p.I1388V), which was predicted to be deleterious by in silico tools. Her healthy parents and sister all carried the heterozygous mutation. Our results provided further support for the association of biallelic SPTAN1 variants with HSP and suggested that screening for the SPTAN1 gene should be considered not only in patients with pure HSP but also in patients with complicated HSP.

SPTAN1中的杂合突变与广泛的表型谱相关，从轴突神经病变表型到伴有或不伴有癫痫的神经发育表型。最近，据报道SPTAN1的双等位基因突变是常染色体隐性遗传性纯遗传性痉挛性截瘫（HSP）的潜在原因。然而，尚未报道具有双等位基因SPTAN1突变的 HSP 病例。在此，我们报告了可能由新型纯合SPTAN1引起的复杂 HSP 患者的临床和遗传学发现突变。招募了一名来自近亲家庭的复杂 HSP 患者。先证者接受了详细的神经系统检查。在先证者和她健康的妹妹中进行了纯合子映射。在先证者中进行全外显子组测序。本例患者早发性运动症状伴上运动神经元麻痹和智力障碍，符合复杂性HSP。遗传分析在 SPTAN1 中发现了一种罕见的纯合错义突变（ c.4162A>G，p.I1388V），据计算机工具预测该突变是有害的。她健康的父母和姐姐都携带了杂合突变。我们的结果为双等位基因SPTAN1变体与 HSP的关联提供了进一步的支持，并建议筛选SPTAN1不仅在单纯 HSP 患者中，在复杂 HSP 患者中也应考虑该基因。