DataSheet1_Case report: A novel FARS2 deletion and a missense variant in a child with complicated, rapidly progressive spastic paraplegia.docx

Defects in FARS2 are associated with either epileptic phenotypes or a spastic paraplegia subtype known as SPG77. Here, we describe an 8-year-old patient with severe and complicated spastic paraplegia, carrying a missense variant (p.Pro361Leu) and a novel intragenic deletion in FARS2. Of note, the disease is unexpectedly progressing rapidly and in a biphasic way differently from the previously reported cases. Our study provides the first detailed molecular characterization of a FARS2 deletion and its underlying molecular mechanism, and demonstrates the need for combining different tools to improve the diagnostic rate.

FARS2基因缺陷可与癫痫表型或名为SPG77的痉挛性截瘫亚型相关联。本研究报道一例患有重症复合型痉挛性截瘫的8岁患者，其携带FARS2基因的错义变异（p.Pro361Leu）及一种全新的基因内缺失突变。值得注意的是，该患者的疾病呈现出意料之外的快速进展，并以双相病程发展，与此前已报道的病例均不相同。本研究首次对FARS2基因缺失突变及其潜在分子机制进行了详细的分子特征描述，并证实了联合多种检测工具以提升诊断率的必要性。