Tremor-associated Short Tandem Repeat Intermediate and Pathogenic Expansions in Familial Essential Tremor

There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including , , , , , , , , , , , , , and , are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls. The demographic and clinical features among carriers of pathogenic expansions, intermediate repeats and non-carriers were compared. A total of 18 out of 515 (18/515, 3.7%) patients were found to have repeats expansions, including 12 cases (12/515, 2.5%) with intermediate repeat expansions (one , eight , two , one ), and six cases (6/515, 1.2%) with pathogenic expansions (one , one , one , one , one , one ). There were no statistically significant differences in intermediate repeats compared to healthy controls. Furthermore, there were no significant differences in demographics and clinical features among individuals with pathogenic expansions, intermediate repeat expansions carriers and non-carriers. Our study indicates that the intermediate repeat expansion in tremor-associated short tandem repeat expansions does not pose an increased risk for essential tremor, and rare pathogenic expansion carriers have been found in the familial essential tremor cohort. The diagnosis of essential tremor based solely on clinical symptoms remains a challenge in distinguishing it from known short tandem repeat expansions diseases with overlapping clinical-pathological features.