Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2005 Apr;57(4):505-12.
doi: 10.1002/ana.20424.

Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort

Bart P C van de Warrenburg  1 , Harrie Hendriks, Alexandra Dürr, Martin C A van Zuijlen, Giovanni Stevanin, Agnès Camuzat, Richard J Sinke, Alexis Brice, Berry P H Kremer
Affiliations
Comparative Study

Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort

Bart P C van de Warrenburg et al. Ann Neurol. 2005 Apr.

Abstract

In dominant spinocerebellar ataxias (SCAs), the issue of whether non-CAG dependent factors contribute to onset age remains unsettled. Data on SCA genotype, onset age, normal/expanded CAG repeat length, sex of the patient and transmitting parent, and family details were available from 802 patients. Based on the model [log(10) (age at onset) = k - b CAG(exp) + epsilon], we examined changes in adjusted R(2) and residual standard error following incorporation of the other factors in this model. The expanded repeat explained 44.3 to 74.9% of onset age variance, although this was less than 50% in SCA3 and SCA6, implicating a large effect of non-CAG factors. The relation between onset age and CAG repeat was similar for SCA1, 3, 6, and 7, but different for SCA2, pointing to different polyglutamine effects in SCA2. For SCA2 and SCA3, 17.1 and 45.5% of onset age variance, respectively, were explained by currently (unidentified) familial factors. We found a significant contribution of the nonexpanded allele in SCA1 and SCA6. Besides polyglutamine motif (determined by the expanded CAG repeat length), we identified the following age at onset modifiers: protein context in SCA2; familial factors in SCA2 and SCA3; and the nonexpanded CAG repeat in SCA1 and SCA6.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources