Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6

Sophie Tezenas du Montcel, Alexandra Durr, Maria Rakowicz, Lorenzo Nanetti, Perrine Charles, Anna Sulek, Caterina Mariotti, Rafal Rola, Ludger Schols, Peter Bauer, Isabelle Dufaure-Garé, Heike Jacobi, Sylvie Forlani, Tanja Schmitz-Hübsch, Alessandro Filla, Dagmar Timmann, Bart P. van de Warrenburg, Cecila Marelli, Jun Suk Kang, Paola GiuntiArron Cook, Laszlo Baliko, Melegh Bela, Sylvia Boesch, Sandra Szymanski, José Berciano, Jon Infante, Katrin Buerk, Marcella Masciullo, Roberto Di Fabio, Chantal Depondt, Susanne Ratka, Giovanni Stevanin, Thomas Klockgether, Alexis Brice, Jean Louis Golmard

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25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalJournal of medical genetics
Issue number7
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    du Montcel, S. T., Durr, A., Rakowicz, M., Nanetti, L., Charles, P., Sulek, A., Mariotti, C., Rola, R., Schols, L., Bauer, P., Dufaure-Garé, I., Jacobi, H., Forlani, S., Schmitz-Hübsch, T., Filla, A., Timmann, D., van de Warrenburg, B. P., Marelli, C., Kang, J. S., ... Golmard, J. L. (2014). Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6. Journal of medical genetics, 51(7), 479-486.