title: TCF4 deletions in Pitt-Hopkins Syndrome.
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.
authors.affiliation: INSERM U841, IMRB, Département de Génétique, Equipe 11, Créteil, F-94000, France. irina.giurgea@inserm.fr
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Chantal
authors.initials: C
authors.lastname: Missirian
authors.forename: Pierre
authors.initials: P
authors.lastname: Cacciagli
authors.forename: Sandra
authors.initials: S
authors.lastname: Whalen
authors.forename: Tessa
authors.initials: T
authors.lastname: Fredriksen
authors.forename: Thierry
authors.initials: T
authors.lastname: Gaillon
authors.forename: Julia
authors.initials: J
authors.lastname: Rankin
authors.forename: Michele
authors.initials: M
authors.lastname: Mathieu-Dramard
authors.forename: Gilles
authors.initials: G
authors.lastname: Morin
authors.forename: Dominique
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Arfi
authors.forename: Fabienne
authors.initials: F
authors.lastname: Giuliano
authors.forename: Jean
authors.initials: J
authors.lastname: Claude Lambert
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002887:Chromosomes, Human, Pair 18; D018388:Codon, Terminator; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006801:Humans; D006985:Hyperventilation / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010641:Phenotype; D017384:Sequence Deletion; D013577:Syndrome; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D018388:Codon, Terminator; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein