title: Fast course ALS presenting with vocal cord paralysis: clinical features, bioinformatic and modelling analysis of the novel SOD1 Gly147Ser mutation.
abstract: In this report we describe a novel SOD1 mutation (Gly147Ser) in an Italian sporadic ALS patient. The patient presented with hoarseness due to bilateral vocal cord paralysis and a rapid clinical course. Mutational analysis of the SOD1 gene was carried out by direct sequencing. In silico bioinformatics analysis and molecular modelling was used to analyse the SOD1 function modifications produced by the mutated residue. A heterozygous c.442 G > A transition, which leads to a change at codon 147 resulting in a serine rather than glycine, was found in the patient. Bioinformatics analysis and molecular modelling strongly suggest a dramatic effect of Gly147Ser mutation on SOD1 function. In conclusion, Gly147Ser represent a new missense mutation whose effect may correlate with the peculiar clinical bulbar phenotype onset with bilateral vocal cord paresis and rapid clinical course of the disease. Ethical and psychological dilemmas about genetic testing in apparently sporadic subjects are still matter of debate.
authors.affiliation: Department of Biology and Genetics, University of Genoa and U.O.C. Medical Genetics of Azienda Ospedaliera Universitaria S. Martino di Genova, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.forename: Vittorio
authors.initials: V
authors.lastname: Mantero
authors.forename: Elena
authors.initials: E
authors.lastname: Cichero
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Geroldi
authors.forename: Simonetta
authors.initials: S
authors.lastname: Verdiani
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D019295:Computational Biology; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D011487:Protein Conformation; D016415:Sequence Alignment; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014826:Vocal Cord Paralysis / Q000209:etiology*
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1