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Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/73707

Type: Journal article
Title: 14q12 and severe Rett-like phenotypes: new clinical insights and physical mapping of FOXG1-regulatory elements
Author: Allou, Lila
Lambert, Laetitia
Amsallem, Daniel
Bieth, Eric
Edery, Patrick
Destree, Anne
Rivier, Francois
Amor, David J.
Thompson, Elizabeth Mary
Nicholl, Julian
Harbord, Michael G.
Nemos, Christophe
Saunier, Aline
Moustaine, Aissa
Vigouroux, Adeline
Jonveaux, Philippe
Philippe, Christophe
Citation: European Journal of Human Genetics, 2012; 27 June:8 p.
Publisher: Nature Publishing Group
Issue Date: 2012
ISSN: 1018-4813
School/Discipline: School of Paediatrics and Reproductive Health : Paediatrics
Statement of
Responsibility: 
Lila Allou, Laetitia Lambert, Daniel Amsallem, Eric Bieth, Patrick Edery, Anne Destrée, François Rivier, David Amor, Elizabeth Thompson, Julian Nicholl, Michael Harbord, Christophe Nemos, Aline Saunier, Aissa Moustaïne, Adeline Vigouroux, Philippe Jonveaux and Christophe Philippe
Abstract: The Forkhead box G1 (FOXG1) gene has been implicated in severe Rett-like phenotypes. It encodes the Forkhead box protein G1, a winged-helix transcriptional repressor critical for forebrain development. Recently, the core FOXG1 syndrome was defined as postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and dysgenesis of the corpus callosum. We present seven additional patients with a severe Rett-like neurodevelopment disorder associated with de novo FOXG1 point mutations (two cases) or 14q12 deletions (five cases). We expand the mutational spectrum in patients with FOXG1-related encephalopathies and precise the core FOXG1 syndrome phenotype. Dysgenesis of the corpus callosum and dyskinesia are not always present in FOXG1-mutated patients. We believe that the FOXG1 gene should be considered in severely mentally retarded patients (no speech-language) with severe acquired microcephaly (−4 to−6 SD) and few clinical features suggestive of Rett syndrome. Interestingly enough, three 14q12 deletions that do not include the FOXG1 gene are associated with phenotypes very reminiscent to that of FOXG1-mutation-positive patients. We physically mapped a putative long-range FOXG1-regulatory element in a 0.43 Mb DNA segment encompassing the PRKD1 locus. In fibroblast cells, a cis-acting regulatory sequence located more than 0.6 Mb away from FOXG1 acts as a silencer at the transcriptional level. These data are important for clinicians and for molecular biologists involved in the management of patients with severe encephalopathies compatible with a FOXG1-related phenotype.
Keywords: 14q12; CNV; FOXG1; Rett syndrome; cis-acting regulatory element
Description: Advance online publication 27 June 2012
Rights: © 2012 Macmillan Publishers Limited All rights reserved
RMID: 0020122026
DOI: 10.1038/ejhg.2012.127
Appears in Collections:Paediatrics Publications
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