trinucleotide repeat diseases
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?.
Classification
(CGG repeats)
- X fragile (FRAXA)
- X fragile (FRAXF)
- FRA11B (Jacobsen syndrome)
(GCC repeats)
- X fragile (FRAXB)
(CCG repeats)
- FRA16A
(GAA repeats)
- Friedreich ataxia (FRDA) (Frataxine)
(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 |
References
Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci. 2007;30:575-621. Review. PMID: 17417937
Gatchel JR, Zoghbi HY. Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet. 2005 Oct;6(10):743-55. PMID: 16205714
Pearson CE, Edamura KN, Cleary JD. Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet. 2005 Oct;6(10):729-42. PMID: 16205713
Di Prospero NA, Fischbeck KH. Therapeutics development for triplet repeat expansion diseases. Nat Rev Genet. 2005 Oct;6(10):756-65. PMID: 16205715
Albrecht A, Mundlos S. The other trinucleotide repeat: polyalanine expansion disorders. Curr Opin Genet Dev. 2005 Jun;15(3):285-93. PMID: 15917204
Cleary JD, Pearson CE. Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability. Trends Genet. 2005 May;21(5):272-80. PMID: 15851063
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
Cummings CJ, Zoghbi HY. Fourteen and counting: unraveling trinucleotide repeat diseases. Hum Mol Genet. 2000 Apr 12;9(6):909-16. PMID: 10767314
Paulson HL, Fischbeck KH. Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci. 1996;19:79-107. PMID: 8833437