GC-rich repeat expansions: associated disorders and mechanisms

Abstract Noncoding repeat expansions are a well-known cause of genetic disorders mainly affecting the central nervous system. Missed by most standard technologies used in routine diagnosis, pathogenic noncoding have to be searched for using specific techniques such as repeat-primed PCR or bioinformatics tools applied genome data, ExpansionHunter. In this review, we focus on GC-rich expansions, which represent at least one third all described so far. located regulatory regions (promoter, 5′ untranslated region, first intron) genes and can lead either toxic gain-of-function mediated RNA toxicity and/or repeat-associated non-AUG (RAN) translation, loss-of-function associated gene, depending their size methylation status. We herein review clinical molecular characteristics with these difficult-to-detect expansions.