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

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.

Automated summary

In this study, an 8-year-old patient with severe and complicated spastic paraplegia was found to carry a missense variant and a novel intragenic deletion in the FARS2 gene. The disease in this patient progressed rapidly and in a biphasic way, which differs from previously reported cases. This study provides a detailed molecular characterization of a FARS2 deletion and highlights the importance of combining different tools to improve the diagnostic rate.