Some of the problems in trinucleotide repeat syndromes result from causing alterations in the coding region of the gene, while others are caused by altered gene regulation. In over half of these<unk> s, the repeated trinucleotide, or codon, is CAG. In a coding region, CAG codes for glutamine (Q), so CAG repeats result in a polyglutamine tract. These diseases are commonly referred to as polyglutamine (or polyQ) diseases. The repeated codons in the remaining<unk> s do not code for glutamine, and these are classified as non-polyglutamine diseases. Polyglutamine (PolyQ) diseases Type Gene Normal PolyQ repeats Pathogenic PolyQ repeats DRPLA (Dentatorubropallidoluysian atrophy) ATN1 or DRPLA 6 - 35 49 - 88 HD (Huntington's disease) HTT 6 - 35 36 - 250 SBMA (Spinal and bulbar muscular atrophy) AR 4 - 34 35 - 72 SCA1 (Spinocerebellar ataxia Type 1) ATXN1 6 - 35 49 - 88 SCA2 (Spinocerebellar ataxia Type 2) ATXN2 14 - 32 33 - 77 SCA3 (Spinocerebellar ataxia Type 3 or Machado-Joseph disease) ATXN3 12 - 40 55 - 86 SCA6 (Spinocerebellar ataxia Type 6) CACNA1A 4 - 18 21 - 30 SCA7 (Spinocerebellar ataxia Type 7) ATXN7 7 - 17 38 - 120 SCA12 (Spinocerebellar ataxia Type 12) PPP2R2B 7 - 41 43 - 51 SCA17 (Spinocerebellar ataxia Type 17) TBP 25 - 42 47 - 63 Non-polyglutamine diseases Type Gene Codon Normal Pathogenic Mechanism FRAXA (Fragile X syndrome) FMR1 CGG (5' UTR) 6 - 53 230+ abnormal methylation FXTAS (Fragile X-associated tremor/ataxia syndrome) FMR1 CGG (5' UTR) 6 - 53 55-200 increased expression, and a novel polyglycine product FRAXE (Fragile XE mental retardation) AFF2 CCG (5' UTR) 6 - 35 200+ abnormal methylation Baratela-Scott syndrome XYLT1 GGC (5' UTR) 6 - 35 200+ abnormal methylation FRDA (Friedreich's ataxia) FXN GAA (Intron) 7 - 34 100+ impaired transcription DM1 (Myotonic dystrophy Type 1) DMPK CTG (3' UTR) 5 - 34 50+ RNA-based; unbalanced DMPK/ZNF9 expression levels SCA8 (Spinocerebellar ataxia Type 8) SCA8 CTG (RNA) 16 - 37 110 - 250 ? RNA
Trinucleotide repeat disorder
Lysosomal storage disease
Ribosomopathy
Lipid storage disorder
Trinucleotide repeat expansion
Creatine transporter defect
Cerebral creatine deficiency
Peroxisomal disorder