TY  - JOUR
A1  - Montcel, Sophie Tezenas du
A1  - Durr, Alexandra
A1  - Rakowicz, Maria
A1  - Nanetti, Lorenzo
A1  - Charles, Perrine
A1  - Sulek, Anna
A1  - Mariotti, Caterina
A1  - Rola, Rafal
A1  - Schols, Ludger
A1  - Bauer, Peter
A1  - Dufaure-Garé, Isabelle
A1  - Jacobi, Heike
A1  - Forlani, Sylvie
A1  - Schmitz-Hübsch, Tanja
A1  - Filla, Alessandro
A1  - Timmann, Dagmar
A1  - Warrenburg, Bart P. van de
A1  - Marelli, Cecila
A1  - Kang, Jun-Suk
A1  - Giunti, Paola
A1  - Cook, Arron
A1  - Baliko, Laszlo
A1  - Bela, Melegh
A1  - Boesch, Sylvia
A1  - Szymanski, Sandra
A1  - Berciano, José
A1  - Infante, Jon
A1  - Buerk, Katrin
A1  - Masciullo, Marcella
A1  - Di Fabio, Roberto
A1  - Depondt, Chantal
A1  - Ratka, Susanne
A1  - Stevanin, Giovanni
A1  - Klockgether, Thomas
A1  - Brice, Alexis
A1  - Golmard, Jean-Louis
T1  - Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6
T2  - Journal of medical genetics
N2  - Background: 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.
Methods: 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.
Results: 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% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age.
Conclusions: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/34402
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-344021
SN  - 1468-6244
SN  - 0022-2593
N1  - This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
VL  - 51
IS  - 7
SP  - 479
EP  - 486
PB  - BMJ Publishing Group
CY  - London
ER  -