In Huntington chorea the causative mutation in the protein huntingtin is a
Trinucleotide repeat expansion
Gene deletion
Frameshift mutation
Point mutation
Expansion of trinucleotide repeats is an important genetic cause of human disease, particularly neurodegenerative disorders. There are three key mechanisms by which unstable repeats cause diseases:
• Loss of function of the affected gene occurs in fragile X syndrome. In such cases the repeats are generally in noncoding part of the gene.
• A toxic gain of function by alterations of protein structure as in Huntington disease and spinocerebellar ataxias. In such cases the expansions occur in the coding regions of the genes.
• A toxic gain of function mediated by mRNA as is seen in fragile X tremor-ataxia syndrome. In this condition, the non coding parts of the gene are affected.