title: Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis.
abstract: Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia. Ubiquilin-2 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. All the previously reported UBQLN2 mutations were localized in 1 of the 12 PXX domains of ubiquilin-2 protein. We sequenced UBQLN2 in 130 French patients with familial ALS (FALS) and absence of male-to-male transmission and the PXX domain in 240 more patients with sporadic ALS (SALS). We identified, at the heterozygote state, the c.1500_1508delCATAGGCCC, p.Gly502_Ile504del, in 1 affected woman. This deletion presumably leads to the in-frame deletion of 1 PXX repeat in the protein. This variant did not segregate with the disease in the corresponding family and was also detected in 1/380 control subject. Our results suggest that UBQLN2 gene mutations are rare in French ALS.
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, INSERM UMR_S975, CNRS UMR7225, Université Pierre et Marie Curie-Paris, Hôpital Pitié-Salpêtrière, Paris, France. stephanie.millecamps@upmc.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Millecamps
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: Séverine
authors.initials: S
authors.lastname: Boillée
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Véronique
authors.initials: V
authors.lastname: Danel-Brunaud
authors.forename: Nadia
authors.initials: N
authors.lastname: Vandenberghe
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Nadine
authors.initials: N
authors.lastname: Le Forestier
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bruneteau
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Eric
authors.initials: E
authors.lastname: LeGuern
authors.forename: François
authors.initials: F
authors.lastname: Salachas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins; C405662:UBQLN2 protein, human; D014452:Ubiquitins