Short tandem repeats (STRs) are a class of repetitive elements, composed of tandem arrays of 1–6 base pair sequence motifs, that comprise a substantial fraction of the human genome. STR expansions can cause a wide range of neurological and neuromuscular conditions, known as repeat expansion disorders, whose age of onset, severity, penetrance and/or clinical phenotype are influenced by the length of the repeats and their sequence composition. The presence of non-canonical motifs, depending on the type, frequency and position within the repeat tract, can alter clinical outcomes by modifying somatic and intergenerational repeat stability, gene expression and mutant transcript-mediated and/or protein-mediated toxicities. Here, we review the diverse structural conformations of repeat expansions, technological advances for the characterization of changes in sequence composition, their clinical correlations and the impact on disease mechanisms.

短串联重复 (STR) 是一类重复元件，由 1-6 个碱基对序列基序的串联阵列组成，构成了人类基因组的很大一部分。 STR 扩增可引起多种神经和神经肌肉疾病，称为重复扩增障碍，其发病年龄、严重程度、外显率和/或临床表型受重复长度及其序列组成的影响。非规范基序的存在，取决于重复序列内的类型、频率和位置，可以通过改变体细胞和代际重复稳定性、基因表达和突变转录介导和/或蛋白质介导的毒性来改变临床结果。在这里，我们回顾了重复扩增的不同结构构象、序列组成变化特征的技术进步、它们的临床相关性以及对疾病机制的影响。