• Cinzia Gellera, Cinzia Tiloca, Roberto Del Bo, Lucia Corrado, Viviana Pensato, Jennifer Agostini, Cristina Cereda, Antonia Ratti, Barbara Castellotti, Stefania Corti, Alessandra Bagarotti, Annachiara Cagnin, Pamela Milani, Carlo Gabelli, Giulietta Riboldi, Letizia Mazzini, Gianni Sorarù, Sandra D'Alfonso, Franco Taroni, Giacomo Pietro Comi, Nicola Ticozzi, Vincenzo Silani, and SLAGEN Consortium.
• Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, Milan, Italy.
• J. Neurol. Neurosurg. Psychiatr. 2013 Feb 1; 84 (2): 183-7.

ObjectivesAmyotrophic 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

22 keywords...

hide…