title: Matrin 3 variants are frequent in Italian ALS patients.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neurons in the primary motor cortex, brainstem, and spinal cord. Recently, missense variants in MATR3 were identified in familial and sporadic ALS patients, but very few additional ALS patients have been reported so far. The p.S85C MATR3 variant was previously associated to a different phenotype, namely a distal myopathy associated with dysphagia and dysphonia. Here, we assessed the contribution of MATR3 variants in a cohort of 322 Italian ALS patients. We identified 5 different missense MATR3 variants (p.Q66K, p.G153C, p.E664A, p.S707L, and p.N787S) in 6 patients (1.9%). None of our patients showed signs of myopathy at electrophysiological examination. Muscle biopsy, performed in 2 patients, showed neurogenic changes and normal nuclear staining with anti-matrin 3 antibody. Our results confirm that MATR3 variants are associated with ALS and suggest that they are more frequent in Italian ALS patients. Further studies are needed to elucidate the pathogenic significance of identified variants in sporadic and familial ALS.
authors.affiliation: Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.affiliation: Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Lattante
authors.affiliation: Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: Paolo Niccolò
authors.initials: PN
authors.lastname: Doronzio
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Conte
authors.affiliation: Don Carlo Gnocchi ONLUS Foundation, Milan, Italy; Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tasca
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Monforte
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Agata Katia
authors.initials: AK
authors.lastname: Patanella
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bisogni
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Institute of Neurology, Catholic University School of Medicine, Rome, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Meleo
authors.affiliation: Neurological Department, Perrino Hospital, Brindisi, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: La Spada
authors.affiliation: Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Institute of Neurology, Catholic University School of Medicine, Rome, Italy. Electronic address: msabatelli@rm.unicatt.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins
keywords: Amyotrophic lateral sclerosis; Distal myopathy; Matrin 3; Targeted NGS sequencing