Trinucleotide Repeat Expansions: Mechanisms and Disease Associations


Trinucleotide (and selected other) repeat expansions may cause severe neurodegenerative disorders with adult onset. Either elongated polyglutamine/polyalanine blocks, toxic polyglutamine peptides or reduced gene expression are responsible for the differential pathogenesis of this rather novel disease category.

Keywords: DNA expansion; neurodegeneration; dynamic mutation; simple repetitive DNA; trinucleotide repeats

Figure 1.

Schematic representation of genes and their trinucleotide blocks involved in selected repeat expansion diseases other than polyglutamine disorders (black bars, protein coding parts). Detailed exon–intron structures of the genes are not shown or have been minimized to demonstrate intronic localization of the repeat blocks. The physiological length ranges of the polymorphic simple repeat tracts are enumerated in the tips of the inverted triangles (grey), whereas the pathological range is annotated in the darkly shaded top portion of each triangle.



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Further Reading

Albrecht A and Mundlos S (2005) The other trinucleotide repeat: polyalanine expansion disorders. Current Opinion in Genetics and Development 15(3): 285–293.

Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) (AR); LocusID: 367. Entrez Gene: & cmd=Retrieve & dopt=summary & list_uids=367

Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) (AR); MIM number: 313700. OMIM:

Cystatin B (stefin B) (CSTB); LocusID: 1476. Entrez Gene: & cmd=Retrieve & dopt=summary & list_uids=1476

Cystatin B (stefin B) (CSTB); MIM number: 601145. OMIM:

Fragile X mental retardation 1 (FMR1); LocusID: 2332. Entrez Gene: & cmd=Retrieve & dopt=summary & list_uids=2332

Fragile X mental retardation 1 (FMR1); MIM number: 309550. OMIM:

Friedreich ataxia (FRDA); LocusID: 2395. Entrez Gene: & cmd=Retrieve & dopt=summary & list_uids=2395

Friedreich ataxia (FRDA); MIM number: 606829. OMIM:

Gatchel JR and Zoghbi HY (2005) Diseases of unstable repeat expansion: mechanisms and common principles. Nature Reviews Genetics 6(10): 743–755.

Spinocerebellar ataxia 8 (SCA8); LocusID: 6315. Entrez Gene: & cmd=Retrieve & dopt=summary & list_uids=6315

Spinocerebellar ataxia 8 (SCA8); MIM number: 603680. OMIM:

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Epplen, Jörg T, and Wieczorek, Stefan(Sep 2007) Trinucleotide Repeat Expansions: Mechanisms and Disease Associations. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005067.pub2]