| Disease | Repeat | Mechanism | Mode of Inheritance | Mnemonic |
|---|---|---|---|---|
| Huntington disease | (CAG)n | Exon → Polyglutamine expansion | AD | Caudate has ↓ ACh and GABA |
| Myotonic syndromes | (CTG)n | 3’ UTR → Abnormal mRNA splicing | AD | Cataracts, Toupee (early balding in males), Gonadal atrophy in males, reduced fertility in females |
| Fragile X syndrome | (CGG)n | 5’ UTR → Hypermethylation | XD | Chin (protruding), Giant Gonads |
| Friedreich ataxia | (GAA)n | Intron → ↓ Frataxin (Silencing) | AR | Ataxic GAAit |
Tip
Patients with DM1 demonstrate somatic mosaicism. The CTG expansion is notably unstable in nondividing cells, including skeletal muscle, the brain, and myocardium (repeat lengths are several-fold longer in these cells). In addition, cellular mRNA content typically decreases with mitosis and increases when the cell is not dividing, therefore, cells that remain senescent (eg, myocardial cells) tend to accumulate more mutant mRNAs over time. These processes help explain why patients with DM1 are more likely to develop symptoms as they age, such as cardiac conduction disturbances.