The genetics of ChAc
Neuroacanthocytosis is an umbrella term for diseases that combine neurological features with acanthocytosis. The disorders in this group include the following:
- Chorea-Acanthocytosis (ChAc) (OMIM 200150) (9q21)
- McLeod syndrome (OMIM 314850) (Xp21.2-p21.1)
- Abetalipoproteinemia (OMIM 200100) (4q22-q24)
- Hypobetalipoproteinemia (OMIM 107730) (2p24)
The Monaco Group has also carried out research on McLeod Syndrome.
Chorea-Acanthocytosis (ChAc) is a rare autosomal recessive disorder that is caused by mutations in the CHAC gene, which is found on the chromosome 9 (9q21).
To date, 71 different mutations of the CHAC gene have been identified (18 nonsense, 29 frameshift, 16 splice-site, 3 missense and 3 deletions of one or more exons).
In 2001, researchers in the Monaco Group ChAc research team were part of the group that first identified the novel gene (CHAC) responsible for ChAc. Subsequently, two further studies by the team identified various mutations in the CHAC gene that are implicated in the disorder.
The CHAC gene encodes the protein chorein. The absence of chorein is a characteristic of ChAc. More recently, the ChAc research team has identified and characterised three other human genes whose encoded proteins present a high level of similarity with chorein: VPS13B (also known as COH1), VPS13C and VPS13D. The team is now working on the characterisation of chorein, and of the proteins identified by these three identified genes.
In 2007, the ChAc research team initiated a new project: "Development of new tools for the analysis of chorein and other VPS13 proteins". This project aims to develop biochemical tools that will enable a more precise understanding of the activity of chorein in the brain.