Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits
- Resource Type
- Authors
- Deny Menghini; Carmela Fusco; Orazio Palumbo; Bartolomeo Augello; Maria Teresa Pellico; Giuseppe Merla; Barbara Mandriani; Massimo Carella; Maria Cristina Digilio; Stefano Vicari; Lucia Micale; Paolo Alfieri
- Source
- Subject
- Adult
Male
Williams Syndrome
medicine.medical_specialty
congenital, hereditary, and neonatal diseases and abnormalities
Biology
Article
Epilepsy
Settore MED/39 - NEUROPSICHIATRIA INFANTILE
Genetic linkage
Molecular genetics
Genetics
medicine
Humans
Williams Beuren syndrome
Autistic Disorder
Child
Genetics (clinical)
Genetic Association Studies
RTqPCR
7q11.23
medicine.disease
Phenotype
Frizzled Receptors
haploinsufficiency
DNA-Binding Proteins
qPCR
Child, Preschool
Autism
Medical genetics
Female
Williams syndrome
Chromosome Deletion
Haploinsufficiency
Chromosomes, Human, Pair 7
Transcription Factors
- Language
- English
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.