title: Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations.
abstract: Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, TGIF ( TG-interacting factor), which codes for a transcription factor modulating the signalling pathway of TGF-beta, was previously implicated. We investigated 127 HPE probands by sequencing their TGIF gene and identified the first nonsense mutation reported so far and also a novel missense mutation, in two families that presented a large range of disease severity. The low number of mutations in TGIF suggests that this gene has no major contribution to the aetiology of HPE and our study confirms the wide clinical heterogeneity of the disease.
authors.affiliation: Service de Génétique Médicale, CHU Pontchaillou, Rennes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Aguilella
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Attia-Sobol
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vigneron
authors.forename: Martine
authors.initials: M
authors.lastname: Blayau
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.forename: Leila
authors.initials: L
authors.lastname: Lazaro
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Véronique
authors.initials: V
authors.lastname: David
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018389:Codon, Nonsense / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus / Q000473:pathology; D005801:Genes, Homeobox / Q000235:genetics*; D016142:Holoprosencephaly / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human; D004247:DNA