title: Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits.
abstract: Williams Beuren syndrome (WBS) is a multisystemic disorder caused by a hemizygous deletion of 1.5 Mb on chromosome 7q11.23 spanning 28 genes. A few patients with larger and smaller WBS deletion have been reported. They show clinical features that vary between isolated SVAS to the full spectrum of WBS phenotype, associated with epilepsy or autism spectrum behavior. Here we describe four patients with atypical WBS 7q11.23 deletions. Two carry ~3.5 Mb larger deletion towards the telomere that includes Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxigenase activation protein gamma (YWHAG) genes. Other two carry a shorter deletion of ~1.2 Mb at centromeric side that excludes the distal WBS genes BAZ1B and FZD9. Along with previously reported cases, genotype-phenotype correlation in the patients described here further suggests that haploinsufficiency of HIP1 and YWHAG might cause the severe neurological and neuropsychological deficits including epilepsy and autistic traits, and that the preservation of BAZ1B and FZD9 genes may be related to mild facial features and moderate neuropsychological deficits. This report highlights the importance to characterize additional patients with 7q11.23 atypical deletions comparing neuropsychological and clinical features between these individuals to shed light on the pathogenic role of genes within and flanking the WBS region.
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fusco
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Micale
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Augello
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Teresa Pellico
authors.affiliation: Child NeuroPsychiatry Unit, Neuroscience Department, IRCCS Children Hospital Bambino Gesù, Rome, Italy.
authors.forename: Deny
authors.initials: D
authors.lastname: Menghini
authors.affiliation: Child NeuroPsychiatry Unit, Neuroscience Department, IRCCS Children Hospital Bambino Gesù, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Alfieri
authors.affiliation: Medical Genetics, IRCCS Children Hospital Bambino Gesù, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cristina Digilio
authors.affiliation: 1] Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy [2] Biomedical Sciences and Translational Medicine, University of Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mandriani
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.affiliation: Child NeuroPsychiatry Unit, Neuroscience Department, IRCCS Children Hospital Bambino Gesù, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicari
authors.affiliation: 1] Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy [2] Reproduction and Development Sciences, University of Trieste, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Merla
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004827:Epilepsy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D014157:Transcription Factors / Q000235:genetics; D018980:Williams Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000092468:Bromodomain Containing Proteins
chemical_list: D004268:DNA-Binding Proteins; D051157:Frizzled Receptors; D014157:Transcription Factors; C116750:BAZ1B protein, human; D000092468:Bromodomain Containing Proteins; C549560:FZD9 protein, human; C073368:HIP1 protein, human