Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions. Over 400 HSP families were recruited to the 100KGP. In order to obtain genetic diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic variants using candidate variants from the Exomiser analysis of the genome sequencing data. A significant gene-disease association was identified for UBAP1 and HSP. Three protein truncating variants were identified in 13 patients from 7 families. All patients presented with juvenile form of pure HSP, with median age at onset 10 years, showing autosomal dominant inheritance or de novo occurrence. Additional clinical features included parkinsonism and learning difficulties, but their association with UBAP1 needs to be established.

遗传性痉挛性截瘫（HSP）是一组以下肢痉挛为特征的异质性遗传性退行性疾病。50％的HSP患者仍未进行遗传诊断。100,000个基因组计划（100KGP）是英国范围内的一项大型计划，旨在为以前未被诊断的患者和状况罕见的家庭提供基因诊断。100KGP招募了400多个HSP家庭。为了获得遗传诊断，使用来自基因组测序数据的Exomiser分析的候选变体对稀有的，预测的病原体进行了基于基因的负担测试。UBAP1的一个重要的基因疾病关联被确定。和HSP。在来自7个家庭的13位患者中鉴定出3个蛋白质截短变体。所有患者均呈少年形式的纯HSP，发病年龄中位数为10岁，显示常染色体显性遗传或从头发生。其他临床特征包括帕金森氏症和学习困难，但需要确定其与UBAP1的关联。