Abstract

With great interest, we read the article by Rickman et al. (2020), highlighting the link between defective phosphatidylethanolamine (PE) biosynthesis and hereditary spastic paraplegia (HSP). The cytidine diphosphate (CDP)-ethanolamine pathway is a three-step enzymatic cascade involved in PE biosynthesis. The rate-limiting enzyme in this pathway, ethanolamine-phosphate cytidylyltransferase (ET), is encoded by PCYT2 (OMIM 618770), and biallelic variants in this gene have been associated with a clinical spectrum of HSP (Vaz et al., 2019; Vélez-Santamaría et al., 2020). Selenoprotein 1 (SELENOI) (OMIM 607915, also known as EPT1), catalyses the final step in the biosynthesis of PE via the CDP-ethanolamine pathway (Horibata and Hirabayashi, 2007). Biallelic variants in SELENOI/EPT1 have also been linked to complex HSP in two families (Ahmed et al., 2017; Horibata et al., 2018). Here, we report two additional individuals harbouring biallelic variants of PCYT2 and SELENOI/EPT1.