@article{10902/32402,
year = {2014},
url = {https://hdl.handle.net/10902/32402},
abstract = {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.},
organization = {This study was supported by grants EUROSCA/LSHM-CT-2004-503304 from the European Union, grant from the European Community's Seventh Framework Programme (FP7/2007-2013 n° 2012-305121 NEUROMICS), GeneMove/01 GM 0503 from the German Ministry of Education and Research, within the framework of the ERA-Net for Research Programmes on Rare Diseases, grant 3 PO5B 019 24 from the Polish Ministry of Scientific Research and Information Technology, and grant No 674N—RISCA/2010—2014 from Polish Ministry of Science and Higher Education. The research leading to these results has received funding from the programme ‘Investissements d'avenir’ ANR-10-IAIHU-06. BPvdW is supported by research grants from the Netherlands Brain Foundation, the Royal Dutch Society for Physical Therapy, BBMRI-NL, and the Radboud University Medical Centre. MB is supported by the grant OTKA K 103983. AF was supported by a grant from POR CREME 2007-20013. AB was supported by the grant EUROSCA/LSHM-CT-2004-503304 and by the grant NEUROMICS (7th framework programme) from the European Union. AB, AD and GS received funding from the VERUM Foundation. AD received support from ANR (French Research Agency) and Eranet for the Risca project, PG and AC work at University College London Hospitals/University College London which receives a proportion of its funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. Paola Giunti receives funding from the EC (HEALTH-F2-2010-242193; FP7 Grant). DeNDRoN, Ataxia UK and NIHR, Department of Health.},
publisher = {BMJ Publishing Group},
publisher = {Journal of Medical Genetics, 2014, 51(7), 479-480},
title = {Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6},
author = {Montcel, Sophie Tezenas du and Durr, Alexandra and Rakowicz, Maria and Nanetti, Lorenzo and Charles, Perrine and Sulek, Anna and Mariotti, Caterina and Rola, Rafal and Schols, Ludger and Bauer, Peter and Dufaure-Garé, Isabelle and Jacobi, Heike and Forlani, Sylvie and Schmitz-Hübsch, Tanja and Filla, Alessandro and Timmann, Dagmar and Warrenburg, Bart P., van de and Marelli, Cecila and Berciano, José Ángel and Infante Ceberio, Jon},
}