Available online 15 April 2024

The highly dynamic nature of the RCF1 locus gives rise to numerous motifs.

The high frequency of the (AAGGG)exp motif presages non-rare genetic disorders.

RFC1-related diseases should be considered as a continuous spectrum phenotype.

Rare heterozygous compound [(AAGGG)exp/loss-of-function variant] are reported.

Biallelic intronic expansions (AAGGG)exp in intron 2 of the RFC1 gene have been shown to be a common cause of late-onset ataxia. Since their first description, the phenotypes, neurological damage, and pathogenic variants associated with the RFC1 gene have been frequently updated. Here, we review the various motifs, genetic variants, and phenotypes associated with the RFC1 gene. We searched PubMed for scientific articles published between March 1st, 2019, and January 15th, 2024. The motifs and phenotypes associated with the RFC1 gene are highly heterogeneous, making molecular diagnosis and clinical screening and investigation challenging. In this review we will provide clues to give a better understanding of RFC1 disease. We briefly discuss new methods for molecular diagnosis, the origin of cough in RFC1 disease, and research perspectives.

RFC1

CANVAS syndrome

Ataxia

DNA repeat expansion

Mutation

Phenotype

© 2024 The Author(s). Published by Elsevier Masson SAS.