WRN and Werner syndrome: To date, nearly 100 different pathogenic variants have been reported in individuals with WS worldwide.2 11 The majority of disease-causing variants in WS result in truncation of the WRN protein and the elimination of the nuclear localisation signal at the C-terminus and/or nonsense-mediated mRNA decay, making them functionally null.2 That most variants result in little to no protein expression seems to be why all individuals with WS share similar phenotypes regardless of the causal variants.