SPG6 accounts for 1% of autosomal dominant Hereditary Spastic Paraplegia (HSP) and is caused by pathogenic variants in NIPA1, which encodes a magnesium transporter located in plasma membrane and early endosomes, implicated in neuronal development and maintenance. Here we report a 39-year-old woman affected by progressive gait disturbance associated to absence seizures episodes within childhood. Clinical exome sequencing identified a likely pathogenic de novo heterozygous variant in NIPA1 (NM_144599.5 c.249 C > G; p.Asn83Lys). Molecular modelling was performed to evaluate putative functional consequence of the NIPA1 protein. Indeed, the Asn83Lys modification is predicted to induce a significant perturbation of the protein structure, altering signal transduction or small-molecule transport by modulating the length of the second transmembrane domain. This is the first study reporting a SPG6-affected patient harbouring the NIPA1 p.Asn83Lys mutation.

SPG6 占常染色体显性遗传性痉挛性截瘫 (HSP) 的 1%，由 NIPA1 中的致病性变异引起，NIPA1编码位于质膜和早期内体中的镁转运蛋白，与神经元发育和维持有关。在这里，我们报告了一名 39 岁的女性，她受到与儿童期失神发作相关的进行性步态障碍的影响。临床外显子组测序确定了NIPA1中可能的致病性从头杂合变异（NM_144599.5 c.249 C > G；p.Asn83Lys）。进行分子建模以评估 NIPA1 蛋白的推定功能结果。事实上，预计 Asn83Lys 修饰会引起蛋白质结构的显着扰动，通过调节第二个跨膜结构域的长度来改变信号转导或小分子转运。这是第一项报告受 SPG6 影响的患者携带NIPA1 p.Asn83Lys 突变的研究。