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trinucleotide repeat diseases

Wednesday 19 November 2003

The pathological expansion of unstable trinucleotide repeats currently is known to cause about 30 diseases (2003). Trinucleotide repeat expansions may prove to cause pathology through a variety of mechanisms including interference with DNA structure, transcription, RNA-protein interaction and altered protein conformations/interactions.

Trinucleotide expansions cause at least 30 diseases. Many are inherited predominantly through paternal transmissions, which are probably the result of germ-cell-specific mutations. A recent study of testicular germ cells in HD patients revealed that expansions occur in diploid cells before the completion of meiosis. Therefore, expansions are not limited to the late-haploid spermatids, in which the genome is ’sleeping’.


- (CGG repeats)

  • X fragile (FRAXA)
  • X fragile (FRAXF)
  • FRA11B (Jacobsen syndrome)

- (GCC repeats)

  • X fragile (FRAXB)

- (CCG repeats)

  • FRA16A

- (GAA repeats)

- (CTG repeats)

  • myotonic dystrophy (DM) (DMPK)
  • spinocerebellar ataxia 8 (SCA8)

- polyglutamine repeat diseases (CAG repeats)

  • Huntington disease
  • Kennedy disease (SBMA)
  • spinocerebellar ataxias (SCA1, SCA2, SCA3, SCA6, SCA7, SCA17)
  • dentatorubral pallidoluysia atrophy (DRPLA)

- polyalanine repeat diseases (GCN repeats)

FOXL2 blepharophimosis-ptosis-epicanthus inversus syndactyly BPES MIM.110100
ZIC2 holoprosencephaly 5 HPE5 MIM.609637
PHOX2B congenital failure of autonomic control - MIM.209880
ARX X-linked infantile spasm syndrome - MIM.308350
SOX3 X-linked mental retardation with isolated growth hormone deficiency MRGH MIM.300123
RUNX2 cleidocranial dysplasia CCD MIM.119600
HOXA13 hand-foot-genital syndrome HFGS MIM.140000
HOXD13 synpolydactyly 1 SPD1 MIM.186000
PABPN1 oculopharyngeal muscular dystrophy OPMD MIM.164300


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- Amiel J, Trochet D, Clement-Ziza M, Munnich A, Lyonnet S. Polyalanine expansions in human. Hum Mol Genet. 2004 Oct 1;13 Suppl 2:R235-43. PMID: 15358730

- Brown LY, Brown SA. Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet. 2004 Jan;20(1):51-8. PMID: 14698619

- Pearson CE. Slipping while sleeping? Trinucleotide repeat expansions in germ cells. Trends Mol Med. 2003 Nov;9(11):490-5. PMID: 14604827

- Nag DK. Trinucleotide repeat expansions: timing is everything.
Trends Mol Med. 2003 Nov;9(11):455-7. PMID: 14604819

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- Paulson HL, Fischbeck KH. Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci. 1996;19:79-107. PMID: 8833437