CAGrepeat

CAGrepeat is a term used to describe expansions of the CAG trinucleotide repeat within genes. In coding regions, CAG encodes the amino acid glutamine, so expanded CAG repeats produce abnormally long polyglutamine (polyQ) tracts in the resulting protein. The length of the CAG tract varies among individuals and can determine whether a gene functions normally or becomes pathogenic. Pathogenic expansions typically exceed a gene-specific threshold, and longer repeats generally correlate with earlier onset and more severe disease in a phenomenon known as anticipation.

CAG repeat expansions cause a subset of neurodegenerative disorders called polyglutamine diseases. The best-known example is Huntington disease, due to expanded repeats in the HTT gene. Other examples include spinocerebellar ataxias such as SCA1 (ATXN1), SCA2 (ATXN2), SCA3/Machado-Joseph disease (ATXN3), SCA6 (CACNA1A), and SCA7 (ATXN7), as well as spinal and bulbar muscular atrophy (SBMA, AR gene) and dentatorubral-pallidoluysian atrophy (DRPLA, ATN1). Most of these conditions are autosomal dominant and exhibit considerable clinical variability.

Diagnosis is based on genetic testing that determines repeat length, typically using PCR and, when necessary, Southern blot. There is no cure; management is supportive and symptom-directed. Research areas include strategies to reduce mutant protein production or its toxicity, such as gene-silencing approaches and therapies targeting protein aggregation.