The genetic abnormality underlying polyQ diseases involves the expansion of CAG trinucleotide repeats within the coding regions of specific genes. The CAG repeat encodes the amino acid glutamine. In healthy individuals, these repeats are present within a normal range. However, in individuals with polyQ diseases, there is an abnormal expansion of CAG repeats beyond the normal range (Table ). -The expansion of CAG repeats occurs in a dynamic and unstable manner, leading to anticipation, a phenomenon where the severity of the disease tends to increase, and the age of onset tends to decrease in successive generations. This phenomenon is often observed in polyQ diseases, resulting in earlier onset and more severe symptoms in subsequent generations. -Eight of the polyQ diseases are inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is sufficient to cause the disease. Therefore, individuals who inherit the expanded CAG repeat from an affected parent have a 50% chance of developing the disease. Exception is SBMA, which is inherited in an X chromosome-linked recessive manner, depending upon male levels of circulating androgens; this aspect of SBMA pathogenesis leads to the disease occurring only in men. -Different polyQ diseases are associated with expansions in different genes. For example: Huntington's disease is caused by an expansion of CAG repeats in the huntingtin (HTT) gene; spinocerebellar ataxias (SCAs) are caused by expansions in various genes, including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7; dentatorubral-pallidoluysian atrophy (DRPLA) is caused by expansions in the ATN1 gene; spinobulbar muscular atrophy (SBMA) is caused by expansions in the androgen receptor (AR) gene. -The length of the polyQ tract (i.e., the number of consecutive glutamine residues) correlates with the age of onset and severity of symptoms in polyQ diseases. Longer polyQ tracts are associated with earlier onset and more severe disease manifestations. In brief, the genetic basis of polyQ diseases involves the expansion of CAG trinucleotide repeats within specific genes, leading to the production of proteins with pathologically long polyglutamine tracts, which contribute to neuronal dysfunction and neurodegeneration.