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TCF4 deletions in Pitt-Hopkins Syndrome.

Irina Giurgea 1, * Chantal Missirian 2 Pierre Cacciagli 2 Sandra Whalen 1 Tessa Fredriksen 1 Thierry Gaillon 1 Julia Rankin 3 Michele Mathieu-Dramard 4 Gilles Morin 4 Dominique Martin-Coignard 5 Christèle Dubourg 6, 7 Brigitte Chabrol 8 Jacqueline Arfi 2 Fabienne Giuliano 9 Jean-Claude Lambert 9 Nicole Philip 2 Pierre Sarda 10 Laurent Villard 2 Michel Goossens 1 Anne Moncla 2
* Corresponding author
1 IMRB - Institut Mondor de recherche biomédicale
2 Département de génétique médicale [Hôpital de la Timone - APHM]
3 Department of Clinical Genetics
4 Service de génétique médicale
5 Service de génétique
6 Service de biologie moléculaire
7 IGDR - Institut de Génétique et Développement de Rennes
8 Service de pédiatrie et neurologie pédiatrique
9 Service de génétique médicale
10 Unité de Génétique Médicale et Foetopathologie
Abstract : Pitt-Hopkins syndrome (PHS) is a probably underdiagnosed, syndromic mental retardation disorder, marked by hyperventilation episodes and characteristic dysmorphism (large beaked nose, wide mouth, fleshy lips, and clubbed fingertips). PHS was shown to be caused by de novo heterozygous mutations of the TCF4 gene, located in 18q21. We selected for this study 30 unrelated patients whose phenotype overlapped PHS but which had been initially addressed for Angelman, Mowat-Wilson, or Rett syndromes. In 10 patients we identified nine novel mutations (four large cryptic deletions, including one in mosaic, and five small deletions), and a recurrent one. So far, a total of 20 different TCF4 gene mutations have been reported, most of which either consist in deletion of significant portions of the TCF4 coding sequence, or generate premature stop codons. No obvious departure was observed between the patients harboring point mutations and large deletions at the 18q21 locus, further supporting TCF4 haploinsufficiency as the molecular mechanism underling PHS. In this report, we also further specify the phenotypic spectrum of PHS, enlarged to behavior, with aim to increase the rate and specificity of PHS diagnosis.
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https://www.hal.inserm.fr/inserm-00325404
Contributor : Hervé de Villemeur <>
Submitted on : Monday, September 29, 2008 - 11:19:21 AM
Last modification on : Thursday, January 14, 2021 - 11:26:42 AM

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Irina Giurgea, Chantal Missirian, Pierre Cacciagli, Sandra Whalen, Tessa Fredriksen, et al.. TCF4 deletions in Pitt-Hopkins Syndrome.. Human Mutation, Wiley, 2008, 29 (11), pp.E242-51. ⟨10.1002/humu.20859⟩. ⟨inserm-00325404⟩

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