P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9

Pamela Magini, Clara Marco-Marin, Juan M Escamilla-Honrubia, Diego Martinelli, Carlo Dionisi-Vici, Francesca Faravelli, Francesca Forzano, Marco Seri, Vicente Rubio, Emanuele Panza

Research output: Contribution to journalArticle

Abstract

In 2015-2016, we and others reported ALDH18A1 mutations causing dominant (SPG9A) or recessive (SPG9B) spastic paraplegia. In vitro production of the ALDH18A1 product, Δ1 -pyrroline-5-carboxylate synthetase (P5CS), appeared necessary for cracking SPG9 disease-causing mechanisms. We now describe a baculovirus-insect cell system that yields mgs of pure human P5CS and that has proven highly valuable with two novel P5CS mutations reported here in new SPG9B patients. We conclude that both mutations are disease-causing, that SPG9B associates with partial P5CS deficiency and that it is clinically more severe than SPG9A, as reflected in onset age, disability, cognitive status, growth, and dysmorphic traits.

Original languageEnglish
Pages (from-to)1533-1540
Number of pages8
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 2019

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    Magini, P., Marco-Marin, C., Escamilla-Honrubia, J. M., Martinelli, D., Dionisi-Vici, C., Faravelli, F., Forzano, F., Seri, M., Rubio, V., & Panza, E. (2019). P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9. Annals of Clinical and Translational Neurology, 6(8), 1533-1540. https://doi.org/10.1002/acn3.50821