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

  • 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.

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Author: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 Giunti, Arron 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
Parent Title (German):Journal of medical genetics
Publisher:BMJ Publishing Group
Place of publication:London
Document Type:Article
Date of Publication (online):2014/04/29
Date of first Publication:2014/04/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/07/31
Page Number:9
First Page:479
Last Page:486
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:
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0