Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. We identified 4 patients with mutations in SPG7 and 3 patients with SPAST mutations, representing 50% of the cohort and indicating a very high diagnostic yield. In the SPG7 group, we identified novel variants in two patients. We have also identified two novel mutations in the SPAST group. We present sequencing data from cDNA and RT-qPCR to support the pathogenicity of these variants, and provide observations regarding the poor genotype-phenotype correlation in these conditions that should be the subject of future study.

遗传性痉挛性截瘫（HSPs）是一组遗传病，其严重程度和发病年龄各不相同。从神经遗传学诊所中，我们鉴定出14例HSP起病很晚的患者，其症状在35岁以后开始。在这一队列中，使用临床可用的HSP测序小组对已知遗传原因进行了测序。我们确定了4例中的突变SPG7 3例和SPAST突变，代表该队列的50％和表示非常高的诊断率。在SPG7组中，我们确定了两名患者的新变异。我们还发现了SPAST中的两个新突变组。我们提供了来自cDNA和RT-qPCR的测序数据以支持这些变异的致病性，并提供了在这些条件下不良基因型-表型相关性的观察结果，这些应作为未来研究的主题。