title: Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B.
abstract: Mutations or deletions involving ZFHX1B (previously SIP1) have recently been found to cause one form of syndromic Hirschsprung disease (HSCR), associated with microcephaly, mental retardation, and distinctive facial features. Patients with the characteristic facial phenotype and severe mental retardation, but without HSCR, have now also been shown to have mutations in this gene. Mutations of ZFHX1B are frequently associated with other congenital anomalies, including congenital heart disease, hypospadias, renal tract anomalies, and agenesis of the corpus callosum (ACC). We present the clinical data and mutation analysis results from a series of 23 patients with this clinical syndrome, of whom 21 have proven ZFHX1B mutations or deletions (15 previously unpublished). Two patients with the typical features (one with and one without HSCR) did not have detectable abnormalities of ZFHX1B. We emphasize that this syndrome can be recognized by the facial phenotype in the absence of either HSCR or other congenital anomalies, and needs to be considered in the differential diagnosis of dysmorphism with severe mental retardation +/- epilepsy.
authors.affiliation: Department of Clinical Genetics, The Children's Hospital at Westmead, Sydney, Australia. merediw@chw.edu.au
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.forename: David
authors.initials: D
authors.lastname: Mowat
authors.forename: Florence
authors.initials: F
authors.lastname: Dastot-Le Moal
authors.forename: Valère
authors.initials: V
authors.lastname: Cacheux
authors.forename: Helena
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: Danny
authors.initials: D
authors.lastname: Cass
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Sharron
authors.initials: S
authors.lastname: Townshend
authors.forename: Cynthia
authors.initials: C
authors.lastname: Curry
authors.forename: Michael
authors.initials: M
authors.lastname: Gattas
authors.forename: Stephen
authors.initials: S
authors.lastname: Braddock
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Kerr
authors.forename: Salim
authors.initials: S
authors.lastname: Aftimos
authors.forename: Harry
authors.initials: H
authors.lastname: Zehnwirth
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrey
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015342:DNA Probes; D004827:Epilepsy / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005260:Female; D006331:Heart Diseases / Q000151:congenital; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D000074165:Zinc Finger E-box Binding Homeobox 2; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D015342:DNA Probes; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2