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  Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model

Innis, J. W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M. E., Williams, T. M., et al. (2004). Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model. Human Molecular Genetics, 13(22), 2841-2851. doi:10.1093/hmg/ddh306.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8789-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-878A-3
Genre: Journal Article
Alternative Title : Hum Mol Gen

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 Creators:
Innis, Jeffrey W., Author
Mortlock, Douglas, Author
Chen, Zhi, Author
Ludwig, Michael, Author
Williams, Melissa E., Author
Williams, Thomas M., Author
Doyle, Colleen D., Author
Shao, Zhihong, Author
Glynn, Michael, Author
Mikulic, Davor, Author
Lehmann, Katarina, Author
Mundlos, Stefan1, Author              
Utsch, Boris, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433557              

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 Abstract: Polyalanine expansions in two of three large imperfect trinucleotide repeats encoded by the first exon of HOXA13 have been reported in hand–foot–genital syndrome (HFGS). Here we report additional families with expansions in the third repeat of 11 and 12 alanine residues, the latter being the largest expansion reported. We also report a patient with a novel, de novo 8-alanine expansion in the first large repeat. Thus, expansions in all three large HOXA13 polyalanine repeats can cause HFGS. To determine the molecular basis for impaired HOXA13 function, we performed homologous recombination in ES cells in mice to expand the size of the third largest polyalanine tract by 10 residues (HOXA13ALA28). Mutant mice were indistinguishable from Hoxa13 null mice. Mutant limb buds had normal steady-state Hoxa13 RNA expression, normal mRNA splicing and reduced levels of steady-state protein. In vitro translation efficiency of the HOXA13ALA28 protein was normal. Thus, loss of function is secondary to a reduction in the in vivo abundance of the expanded protein likely due to degradation.

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Language(s): eng - English
 Dates: 2004-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 228748
DOI: 10.1093/hmg/ddh306
 Degree: -

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Title: Human Molecular Genetics
  Alternative Title : Hum Mol Gen
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 13 (22) Sequence Number: - Start / End Page: 2841 - 2851 Identifier: ISSN: 0964-6906