PT - JOURNAL ARTICLE AU - Ellenore M Martin AU - Ying Zhu AU - Claudine M Kraan AU - Kishore R Kumar AU - David E Godler AU - Michael Field TI - Men with <em>FMR1</em> premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS) AID - 10.1136/jmedgenet-2021-107758 DP - 2021 Jul 27 TA - Journal of Medical Genetics PG - jmedgenet-2021-107758 4099 - http://jmg.bmj.com/content/early/2021/08/04/jmedgenet-2021-107758.short 4100 - http://jmg.bmj.com/content/early/2021/08/04/jmedgenet-2021-107758.full AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset condition characterised by cerebellar ataxia and intention tremor, usually found in individuals with FMR1 premutation alleles (PM—CGG expansion of 55–199 repeats). Population studies estimate that between 1 in 250 and 1 in 1600 men have a PM, with up to 45% of these men suggested to develop FXTAS by age 80. We used a Bayesian approach to compare the probability of finding a specific PM genotype in an ataxia population to a population control group and found an estimated penetrance of &lt;1% (0.031%; CI 0.007% to 0.141%) for men with ≤70 CGGs. These findings suggest that men with a PM of ≤70 CGGs, who comprise the vast majority of those with a PM, have a much lower risk of being affected with FXTAS than previously suggested. This is an issue of growing importance for accurate genetic counselling, as those with a PM of ≤70 CGGs are increasingly detected through community carrier screening or neurodevelopmental assessment programmes.