Fragile X–associated tremor/ataxia syndrome in sisters related to X‐inactivation

Fragile X tremor/ataxia syndrome (FXTAS) is a recently described condition consisting of tremor, ataxia, parkinsonism, and executive dysfunction, presenting predominantly in male carriers of a fragile X mental retardation 1 premutation. In this report, we present premutation carrier sisters in whom severity of clinical signs correlated with a molecular pattern of X‐inactivation favoring higher expression of the premutation allele. In these women with a common genetic background, we suggest that symptom severity may be dictated by X‐inactivation, and thus a higher percentage of cells producing the premutation‐containing mRNA result in increased toxicity and disease. Ann Neurol 2005;57:144–147