title: ZFHX1B mutations in patients with Mowat-Wilson syndrome.
abstract: Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). It is caused by de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes Smad-interacting protein-1 (SMADIP1 or SIP1), a transcriptional corepressor involved in the transforming growth factor-beta signaling pathway. It is a highly evolutionarily conserved gene, widely expressed in embryological development. Over 100 mutations have been described in patients with clinically typical MWS, who almost always have whole gene deletions or truncating mutations (nonsense or frameshift) of ZFHX1B, suggesting that haploinsufficiency is the basis of MWS pathology. No obvious genotype-phenotype correlation could be identified so far, but atypical phenotypes have been reported with missense or splice mutations in the ZFHX1B gene. In this work we describe 40 novel mutations and we summarize the various mutational reports published since the identification of the causative gene.
authors.affiliation: INSERM, U654, Université Paris 12, IFR10-IM3, AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Service de Biochimie et Génétique, Hôpital Henri Mondor, Créteil, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Dastot-Le Moal
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.forename: David
authors.initials: D
authors.lastname: Mowat
authors.forename: Nathalie
authors.initials: N
authors.lastname: Collot
authors.forename: Florence
authors.initials: F
authors.lastname: Niel
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics*; D013577:Syndrome; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2