Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia
Por:
Dols-Icardo, O, Garcia-Redondo, A, Rojas-Garcia, R, Sanchez-Valle, R, Noguera, A, Gomez-Tortosa, E, Pastor, P, Hernandez, I, Esteban-Perez, J, Suarez-Calvet, M, Anton-Aguirre, S, Amer, G, Ortega-Cubero, S, Blesa, R, Fortea, J, Alcolea, D, Capdevila, A, Antonell, A, Llado, A, Munoz-Blanco, JL, Mora, JS, Galan-Davila, L, De Rivera, FJR, Lleo, A, Clarimon, J
Publicada:
1 feb 2014
Resumen:
Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotide repeat number and clinical phenotype. Here we characterize, through a new non-radioactive Southern blot protocol, the expansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of >30 copies of the repeat. Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients (P < 0.05 in all comparisons). A higher median number of repeats correlated with a bigger range of repeat sizes (Spearman's rho = 0.743, P = 1.05 x 10(-11)). We did not find any correlation between age of onset or disease duration with the repeat size in neither ALS nor FTD mutation carriers. Clinical presentation (bulbar or spinal) in ALS patients did not correlate either with the repeat length. We finally analyzed two families with affected and unaffected repeat expansion carriers, compared the size of the repeat expansion between two monozygotic (MZ) twins (one affected of ALS and the other unaffected), and examined the expansion size in two different tissues (cerebellum and peripheral blood) belonging to the same FTD patient. The results suggested that the length of the C9orf72 repeat varies between family members, including MZ twins, and among different tissues from the same individual.
Filiaciones:
Dols-Icardo, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Garcia-Redondo, A:
Hosp 12 Octubre, Dept Neurol, Inst Invest Biomed, ALS Unit, E-28041 Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Sanchez-Valle, R:
Hosp Clin Barcelona, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Inst Neurosci,IDIBAPS, Barcelona, Spain
Noguera, A:
Hosp Univ Son Espases, Dept Clin Anal, Mallorca, Spain
Gomez-Tortosa, E:
Fdn Jimenez Diaz, Dept Neurol, E-28040 Madrid, Spain
Pastor, P:
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Univ Navarra, Neurogenet Lab, Div Neurosci, Ctr Appl Med Res, E-31080 Pamplona, Spain
Univ Navarra, Clin Univ Navarra, Dept Neurol, Sch Med, E-31080 Pamplona, Spain
Hernandez, I:
Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain
Esteban-Perez, J:
Hosp 12 Octubre, Dept Neurol, Inst Invest Biomed, ALS Unit, E-28041 Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Valencia, Spain
Suarez-Calvet, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Anton-Aguirre, S:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Amer, G:
Hosp Univ Son Espases, Dept Neurol, Mallorca, Spain
Ortega-Cubero, S:
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Univ Navarra, Neurogenet Lab, Div Neurosci, Ctr Appl Med Res, E-31080 Pamplona, Spain
Univ Navarra, Clin Univ Navarra, Dept Neurol, Sch Med, E-31080 Pamplona, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Capdevila, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Antonell, A:
Hosp Clin Barcelona, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Inst Neurosci,IDIBAPS, Barcelona, Spain
Llado, A:
Hosp Clin Barcelona, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Inst Neurosci,IDIBAPS, Barcelona, Spain
Munoz-Blanco, JL:
Hosp Univ Gregorio Maranon, Dept Neurol, ALS Unit, Madrid, Spain
Mora, JS:
Hosp Carlos III, Dept Neurol, ALS Unit, Madrid, Spain
Galan-Davila, L:
Hosp Clin Univ San Carlos, Dept Neurol, ALS Unit, Madrid, Spain
De Rivera, FJR:
Hosp Univ La Paz, Dept Neurol, ALS Unit, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
Clarimon, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Neuromuscular Dis Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, E-08193 Barcelona, Spain
Ctr Networking Biomed Res Neurodegenerat Dis CIBE, Madrid, Spain
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