title: Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome.
abstract: Pitt-Hopkins syndrome is a severe congenital encephalopathy recently ascribed to de novo heterozygous TCF4 gene mutations. We report a series of 13 novel PHS cases with a TCF4 mutation and show that EEG, brain magnetic resonance imagain (MRI), and immunological investigations provide valuable additional clues to the diagnosis. We confirm a mutational hot spot in the basic domain of the E-protein. Functional studies illustrate that heterodimerisation of mutant TCF4 proteins with a tissue-specific transcription factor is less effective than that homodimerisation in a luciferase reporter assay. We also show that the TCF4 expression pattern in human embryonic development is widespread but not ubiquitous. In summary, we further delineate an underdiagnosed mental retardation syndrome, highlighting TCF4 function during development and facilitating diagnosis within the first year of life.
authors.affiliation: Unité INSERM U-781, Université Paris Descartes, Faculté de Médecine, INSERM.
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.forename: Yves
authors.initials: Y
authors.lastname: Mathieu
authors.forename: Christelle
authors.initials: C
authors.lastname: Golzio
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Christine
authors.initials: C
authors.lastname: Soufflet
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
authors.forename: Angus
authors.initials: A
authors.lastname: Dobbie
authors.forename: Delphine
authors.initials: D
authors.lastname: Heron
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Jacques
authors.initials: J
authors.lastname: Motte
authors.forename: Ruth
authors.initials: R
authors.lastname: Newburry-Ecob
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Géraldine
authors.initials: G
authors.lastname: Viot
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Heather
authors.initials: H
authors.lastname: Etchevers
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D019281:Dimerization; D004569:Electroencephalography; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D006985:Hyperventilation / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008607:Intellectual Disability / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D008156:Luciferases