title: Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the  ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD.
  
  
  METHODS
  We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only.
  
  
  RESULTS
  We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant.
  
  
  CONCLUSIONS
  Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tiloca
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Lucia
authors.initials: L
authors.lastname: Corrado
authors.forename: Viviana
authors.initials: V
authors.lastname: Pensato
authors.forename: Jennifer
authors.initials: J
authors.lastname: Agostini
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.forename: Antonia
authors.initials: A
authors.lastname: Ratti
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellotti
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bagarotti
authors.forename: Annachiara
authors.initials: A
authors.lastname: Cagnin
authors.forename: Pamela
authors.initials: P
authors.lastname: Milani
authors.forename: Carlo
authors.initials: C
authors.lastname: Gabelli
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.forename: Gianni
authors.initials: G
authors.lastname: Sorarù
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; 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