OBJECTIVES: 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.
OBJECTIVES: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-FTDpatients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS-FTDpatients, while SALS and FTDpatients 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 ALSpatients. 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 SALSpatient. 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: Rosa Capozzo; Celeste Sassi; Monia B Hammer; Simona Arcuti; Chiara Zecca; Maria R Barulli; Rosanna Tortelli; J Raphael Gibbs; Cynthia Crews; Davide Seripa; Francesco Carnicella; Claudia Dell'Aquila; Marco Rossi; Filippo Tamma; Francesco Valluzzi; Bruno Brancasi; Francesco Panza; Andrew B Singleton; Giancarlo Logroscino Journal: Alzheimers Dement Date: 2017-03-03 Impact factor: 21.566
Authors: Nhat T T Le; Lydia Chang; Irina Kovlyagina; Polymnia Georgiou; Nathaniel Safren; Kerstin E Braunstein; Mark D Kvarta; Adam M Van Dyke; Tara A LeGates; Thomas Philips; Brett M Morrison; Scott M Thompson; Adam C Puche; Todd D Gould; Jeffrey D Rothstein; Philip C Wong; Mervyn J Monteiro Journal: Proc Natl Acad Sci U S A Date: 2016-11-09 Impact factor: 11.205
Authors: Thuy P Dao; Brian Martyniak; Ashley J Canning; Yongna Lei; Erica G Colicino; Michael S Cosgrove; Heidi Hehnly; Carlos A Castañeda Journal: Structure Date: 2019-04-11 Impact factor: 5.006