TY  - JOUR
AU  - Tezenas du Montcel, Sophie
AU  - Durr, Alexandra
AU  - Rakowicz, Maria
AU  - Nanetti, Lorenzo
AU  - Charles, Perrine
AU  - Sulek, Anna
AU  - Mariotti, Caterina
AU  - Rola, Rafal
AU  - Schols, Ludger
AU  - Bauer, Peter
AU  - Dufaure-Garé, Isabelle
AU  - Jacobi, Heike
AU  - Forlani, Sylvie
AU  - Schmitz-Hübsch, Tanja
AU  - Filla, Alessandro
AU  - Timmann, Dagmar
AU  - van de Warrenburg, Bart P
AU  - Marelli, Cecila
AU  - Kang, Jun-Suk
AU  - Giunti, Paola
AU  - Cook, Arron
AU  - Baliko, Laszlo
AU  - Melegh, Béla
AU  - Bela, Melegh
AU  - Boesch, Sylvia
AU  - Szymanski, Sandra
AU  - Berciano, José
AU  - Infante, Jon
AU  - Buerk, Katrin
AU  - Masciullo, Marcella
AU  - Di Fabio, Roberto
AU  - Depondt, Chantal
AU  - Ratka, Susanne
AU  - Stevanin, Giovanni
AU  - Klockgether, Thomas
AU  - Brice, Alexis
AU  - Golmard, Jean-Louis
TI  - Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.
JO  - Journal of medical genetics
VL  - 51
IS  - 7
SN  - 0022-2593
CY  - London
PB  - BMJ Publishing Group
M1  - DZNE-2020-03758
SP  - 479-486
PY  - 2014
AB  - The most common spinocerebellar ataxias (SCA)-SCA1, SCA2, SCA3, and SCA6-are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset.We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age.For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90
KW  - Adult
KW  - Age of Onset
KW  - Algorithms
KW  - Female
KW  - Genotype
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Models, Genetic
KW  - Models, Statistical
KW  - Spinocerebellar Ataxias: epidemiology
KW  - Spinocerebellar Ataxias: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:24780882
C2  - pmc:PMC4078703
DO  - DOI:10.1136/jmedgenet-2013-102200
UR  - https://pub.dzne.de/record/137436
ER  -