title: Recurrent ∼100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene, is associated with autism and macrocephaly.
abstract: The most frequent causes of Intellectual Disability (ID)/Autism Spectrum Disorders (ASDs) are chromosomal abnormalities, genomic rearrangements and submicroscopic deletions coupled with duplications. We report here on an 11-year-old girl showing autism, macrocephaly, and facial dysmorphism, in which array-CGH showed a de novo microdeletion of ∼114 Kb in the 14q11.2 chromosomal region, involving the SUPT16H, CHD8, and RAB2B genes. Four patients with ID and/or ASD and/or macrocephaly with overlapping deletions have been previously described: three showed very large rearrangements (>1 Mb), while one had a microdeletion of ∼101 Kb, largely overlapping the one reported herein. The minimal critical region, considering present and previous cases, contains the SUPT16H and CHD8 genes. Notably, recent studies also disclosed CHD8 heterozygous loss-of-function mutations in patients with ASD and macrocephaly. Our finding shows the presence of a recurrent microdeletion associated with a clinically recognizable phenotype, and further on underlines the pivotal role of CHD8 gene in the pathogenesis of the disorder.
authors.affiliation: Centro di Riferimento Regionale di Genetica Medica, Azienda Ospedaliera-Universitaria di Perugia, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Prontera
authors.forename: Valentina
authors.initials: V
authors.lastname: Ottaviani
authors.forename: Daniela
authors.initials: D
authors.lastname: Toccaceli
authors.forename: Daniela
authors.initials: D
authors.lastname: Rogaia
authors.forename: Carmen
authors.initials: C
authors.lastname: Ardisia
authors.forename: Rita
authors.initials: R
authors.lastname: Romani
authors.forename: Gabriela
authors.initials: G
authors.lastname: Stangoni
authors.forename: Angiolo
authors.initials: A
authors.lastname: Pierini
authors.forename: Emilio
authors.initials: E
authors.lastname: Donti
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D058627:Megalencephaly / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C523331:CHD8 protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors
keywords: CHD8 gene; SUPT16H gene; autism; macrocephaly; microdeletion 14q11.2; recurrent syndrome