title: A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient.
abstract: Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype.
authors.affiliation: Department Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont, Novara, Italy. lucia.corrado@med.unipmn.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Corrado
authors.forename: Yari
authors.initials: Y
authors.lastname: Carlomagno
authors.forename: Luca
authors.initials: L
authors.lastname: Falasco
authors.forename: Simona
authors.initials: S
authors.lastname: Mellone
authors.forename: Michela
authors.initials: M
authors.lastname: Godi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cova
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.forename: Lucia
authors.initials: L
authors.lastname: Testa
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods; D004185:Disability Evaluation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064531:Peripherins; D055815:Young Adult
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins