polyalanine repeat diseases
Expansions of trinucleotide repeats encoding polyalanine tracts have been recognized as the cause of several diseases, predominantly congenital malformation syndromes.
In 2005, nine genes with alanine tract expansions have been described.
With the exception of PABPN1, which codes for a poly(A)-binding protein, all these genes encode transcription factors that play important roles during development.
Expansions of polyalanine tracts beyond a certain threshold result in protein misfolding, protein aggregation and subsequent protein degradation.
Polyalanine tracts are relatively common in the genome and occur most frequently in transcription factors and other proteins with nuclear localization.
The molecular role of alanine tracts is unknown, but their strong evolutionary conservation suggests the existence of potent functional or structural constraints.
Types
| 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 |
See also
References
Albrecht A, Mundlos S. The other trinucleotide repeat: polyalanine expansion disorders. Curr Opin Genet Dev. 2005 Jun;15(3):285-93. PMID: 15917204
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