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polyalanine repeat diseases

Friday 23 April 2004

- 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.


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

- trinucleotide repeats


- 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