Repeat Instability in the Fragile X-Related Disorders: Lessons from a Mouse Model

Abstract

The fragile X-related disorders (FXDs) are a group of clinical conditions that result primarily from an unusual mutation, the expansion of a CGG-repeat tract in exon 1 of the FMR1 gene. Mouse models are proving useful for understanding many aspects of disease pathology in these disorders. There is also reason to think that such models may be useful for understanding the molecular basis of the unusual mutation responsible for these disorders. This review will discuss what has been learnt to date about mechanisms of repeat instability from a knock-in FXD mouse model and what the implications of these findings may be for humans carrying expansion-prone FMR1 alleles.

Keywords

• CGG Repeat Expansion Disease
• DNA instability
• expansion
• contraction
• mismatch repair (MMR)
• base excision repair (BER)
• transcription coupled repair (TCR)
• double-strand break repair (DSBR)
• Non-homologous end-joining (NHEJ)
• mosaicism