[Skip to Content]
[Skip to Content Landing]
Citations 0
January 19, 2005

Premutation Alleles and Fragile X–Associated Tremor/Ataxia Syndrome—Reply

JAMA. 2005;293(3):296-297. doi:10.1001/jama.293.3.296-b

In Reply: We agree with Drs Toft and Farrer that premutation carriers identified in the studies by Macpherson et al and Van Esch et al showed clinical features (ataxia and/or intention tremor) and cerebellar white matter abnormalities on imaging that serve as a major diagnostic criterion of FXTAS.1,2 Mutations in the FMR1 gene should be considered in patients with ataxia, but ataxic patients with FXTAS usually have other findings such as cognitive changes, parkinsonism, and abnormal magnetic resonance imaging results that should differentiate FXTAS from spinocerebellar ataxias. Nevertheless, because of the clinical overlap between FXTAS and spinocerebellar ataxia, it is prudent to test for FMR1 premutations, particularly in male patients with familial ataxia in whom the known spinocerebellar ataxias have been excluded. This is supported by a recent study of 122 patients with ataxia who tested negative for spinocerebellar ataxia 1, 2, 3, 6, and 7, but of whom 5 were found to have FMR1 premutations.3 This led those authors to conclude that FMR1 analysis “should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years.” We agree with this recommendation.

First Page Preview View Large
First page PDF preview
First page PDF preview