title: Analysis of hnRNPA1, A2/B1, and A3 genes in patients with amyotrophic lateral sclerosis.
abstract: Mutations in the prion-like domain (PrLD) of hnRNPA1 and A2/B1 genes were recently identified in 2 families with inclusion body myopathy associated with Paget disease of bone, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis, and in ALS patients. These mutations were shown to increase the propensity of hnRNPA1 and A2/B1 proteins, which are TDP-43-binding partners, to self-aggregate. hnRNPA3 protein contains a similar PrLD and was recently described in the p62-positive/TDP-43-negative inclusions in affected tissues of C9orf72-mutated ALS/FTD patients. We screened hnRNPA1, A2/B1, and A3 genes in a cohort of 113 familial ALS (FALS) individuals without mutations in other known ALS-causative genes. We extended our analysis to 108 FALS with mutations in other ALS-associated genes and to 622 sporadic cases by screening specifically the PrLDs of hnRNPA1, A2/B1, and A3. We failed to find variants in each cohort. Our results suggest that mutations in hnRNPA1, A2/B1, and A3 genes are a rare finding in ALS.
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095 Cusano Milanino, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calini
authors.forename: Lucia
authors.initials: L
authors.lastname: Corrado
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Stella
authors.initials: S
authors.lastname: Gagliardi
authors.forename: Viviana
authors.initials: V
authors.lastname: Pensato
authors.forename: Federico
authors.initials: F
authors.lastname: Verde
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.forename: Pamela
authors.initials: P
authors.lastname: Milani
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellotti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bertolin
authors.forename: Gianni
authors.initials: G
authors.lastname: Sorarù
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.forename: John E
authors.initials: JE
authors.lastname: Landers
authors.forename: Antonia
authors.initials: A
authors.lastname: Ratti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005192:Family Health; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics*; D006801:Humans; D008297:Male
chemical_list: D004268:DNA-Binding Proteins; C502034:HNRNPA3 protein, human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C439768:hnRNP A2; C000619656:hnRNPA1 protein, human
keywords: ALS; Genetics; IBMPFD; Prion-like domain; hnRNP