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

doi:10.1002/acn3.50821

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

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1533-1540
Number of pages	8
Journal	Annals of Clinical and Translational Neurology
Volume	6
Issue number	8
DOIs	https://doi.org/10.1002/acn3.50821
Publication status	Published - Aug 2019

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title = "P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9",

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.",

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

note = "{\textcopyright} 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.",

year = "2019",

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doi = "10.1002/acn3.50821",

language = "English",

volume = "6",

pages = "1533--1540",

journal = "Annals of Clinical and Translational Neurology",

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TY - JOUR

T1 - P5CS expression study in a new family with ALDH18A1-associated hereditary spastic paraplegia SPG9

AU - Magini, Pamela

AU - Marco-Marin, Clara

AU - Escamilla-Honrubia, Juan M

AU - Martinelli, Diego

AU - Dionisi-Vici, Carlo

AU - Faravelli, Francesca

AU - Forzano, Francesca

AU - Seri, Marco

AU - Rubio, Vicente

AU - Panza, Emanuele

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

U2 - 10.1002/acn3.50821

DO - 10.1002/acn3.50821

M3 - Article

C2 - 31402623

SN - 2328-9503

VL - 6

SP - 1533

EP - 1540

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 8

ER -

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

Abstract

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