title: Valproate Treatment in an ALS Patient Carrying a c.194G>A Spastin Mutation and SMN2 Homozygous Deletion.
abstract: Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600 mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism. Patient clinical course and molecular effects of VPA on skin fibroblasts obtained from the proband are described. This c.194G>A spastin mutation might expand the previously known borders of type 4 spastic paraplegia (SPG4) and we suggest the intriguing possibility that the absence of SMN2 might have acted as a contributory risk factor for starting lower motor neuron damage. Exploring the relationship genocopy-phenocopy in selected ALS patients might represent an interesting strategy for understanding its clinical variability.
authors.affiliation: Section of Neurology, Ospedale San Gerardo and DCMT, Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Lucio
authors.identifier: 0000-0003-0473-6560
authors.initials: L
authors.lastname: Tremolizzo
authors.affiliation: Section of Neurology, Ospedale San Gerardo and DCMT, Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Gessica
authors.identifier: 0000-0003-3573-7523
authors.initials: G
authors.lastname: Sala
authors.affiliation: Section of Neurology, Ospedale San Gerardo and DCMT, Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Elisa
authors.identifier: 0000-0002-8308-9084
authors.initials: E
authors.lastname: Conti
authors.affiliation: Section of Neurology, Ospedale San Gerardo and DCMT, Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Rodriguez-Menendez
authors.affiliation: Medical Genetics, A.O.U. Pisana, Ospedale Santa Chiara, Pisa, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fogli
authors.affiliation: Medical Genetics, A.O.U. Pisana, Ospedale Santa Chiara, Pisa, Italy.
authors.forename: Angela
authors.identifier: 0000-0003-0173-325X
authors.initials: A
authors.lastname: Michelucci
authors.affiliation: Medical Genetics, A.O.U. Pisana, Ospedale Santa Chiara, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
authors.affiliation: Medical Genetics, Department of Laboratory Medicine, Fondazione Serena, Ospedale Niguarda Ca' Granda, Milano, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena, Ospedale Niguarda Ca' Granda, Milano, Italy.
authors.forename: Christian
authors.identifier: 0000-0002-4788-1875
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Fondazione Serena, Ospedale Niguarda Ca' Granda, Milano, Italy ; Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Corbo
authors.affiliation: Section of Neurology, Ospedale San Gerardo and DCMT, Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Carlo
authors.identifier: 0000-0002-7499-6600
authors.initials: C
authors.lastname: Ferrarese