Premutations in the FMR1 Gene Are Uncommon in Men Undergoing Genetic Testing for Spinocerebellar Ataxia

Abstract

To determine the prevalence of Fragile X-associated Tremor Ataxia Syndrome (FXTAS) among men with undiagnosed ataxic disorders. PCR amplification of CGG repeats in the FMR1 gene and a chart review of clinical features were performed for 286 male subjects who had non diagnostic genetic testing for spinocerebellar ataxia between November 1998 and October 2002 prior to widespread clinical testing of FXTAS. Chart review showed that 55% of tested subjects manifested only one cardinal clinical feature of FXTAS (progressive intention tremor, ataxia, and cognitive decline), 20% had two of the three findings, and 4% had all three. Gait ataxia associated with clinical features not characteristic of FXTAS was reported in 47% of subjects. Molecular analysis yielded one FMR1 premutation (100 CGG repeats). Combining our data with that of comparable published studies shows 17/1,320 (1.3%) males tested for adult-onset ataxia had FMR1 premutations. FMR1 premutations are an uncommon cause of spinocerebellar ataxia. This study is in agreement with other similar studies and supports recommendations that testing be considered only if there are additional supporting clinical features indicating that a possible FMR1 premutation may be involved.

Keywords:

• Ataxia
• Fragile X-associated Tremor Ataxia Syndrome
• FMR1 gene