title: UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis.
abstract: Mutations in the UBQLN2 gene, which encodes a member of the ubiquitin-like protein family (ubiquilin-2), have been recently identified in patients with dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS with dementia. We report here the sequencing of the UBQLN2 gene in 590 ALS patients of French and French-Canadian ancestry. We identified two novel missense mutations (p.S155N and p.P189T) in two individuals with sporadic ALS. Bioinformatic analysis predicts that these missense mutations affect the normal protein's function. Importantly, these findings further highlight the importance of the proline residues located in the conserved domains of the ubiquilin-2 protein, suggesting that mutations affecting these residues are particularly relevant to the development of ALS. Our findings further support a causative role of the UBQLN2 gene in the pathogenesis of ALS and suggest that UBQLN2 mutations are rare in the French and French-Canadian population.
authors.affiliation: Centre of Excellence in Neuroscience of Université de Montréal (CENUM), CHUM Research Center and the Department of Medicine, Montreal, Quebec, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.forename: Hamid
authors.initials: H
authors.lastname: Suhail
authors.forename: Anna
authors.initials: A
authors.lastname: Szuto
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Francois
authors.initials: F
authors.lastname: Salachas
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bouchard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D000071183:Autophagy-Related Proteins; D002170:Canada; D018797:Cell Cycle Proteins / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins; C405662:UBQLN2 protein, human; D014452:Ubiquitins