Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/57755
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Type: Journal article
Title: Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X)
Author: Fullston, T.
Brueton, L.
Willis, T.
Philip, S.
MacPherson, L.
Finnis, M.
Gecz, J.
Morton, J.
Citation: European Journal of Human Genetics, 2010; 18(2):157-162
Publisher: Nature Publishing Group
Issue Date: 2010
ISSN: 1018-4813
1476-5438
Statement of
Responsibility: 
Tod Fullston, Louise Brueton, Tracey Willis, Sunny Philip, Lesley MacPherson, Merran Finnis, Jozef Gecz and Jenny Morton
Abstract: Aristaless-related homeobox (ARX) gene mutations cause a diverse spectrum of disorders of the human brain, including lissencephaly, various forms of epilepsy and non-syndromic mental retardation. We have identified a novel mutation, c.81C>G (p.Y27X), within the ARX gene in a family with two affected male cousins. One of the boys was diagnosed with an early infantile epileptic encephalopathy also known as Ohtahara syndrome, whereas his cousin had been diagnosed with West syndrome (WS). Both patients have normal genitalia and neither have lissencephaly. The ARX mutation identified is predicted to yield a severely truncated protein of only 26 amino acids and can be considered as a null mutation. Somewhat surprisingly, however, it does not yield the X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome. We proposed that the ARX mRNA translation re-initiated at the next AUG codon at position c.121-123 (aa 41) and, thus, partly rescued these patients from XLAG. Our in vitro studies show that this N-terminally truncated ARX protein (p.M41_C562) is detected by western immunoblot in lysates from cells transiently transfected with an ARX over-expression construct containing the c.81C>G mutation. Although these findings widen the spectrum of clinical phenotypes because of mutations in the ARX gene, they also emphasize the molecular pathogenetic effect of individual mutations as well as the effect of genetic background resulting in intrafamilial clinical heterogeneity for these mutations.
Keywords: Ohtahara syndrome; burst suppression; ARX gene; West syndrome
Description: Published online 9 September 2009 © 2010 European Society of Human Genetics
RMID: 0020093652
DOI: 10.1038/ejhg.2009.139
Appears in Collections:Paediatrics publications

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