title: A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.
abstract: Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity.
authors.affiliation: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Biamino
authors.affiliation: Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Di Gregorio
authors.affiliation: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
authors.forename: Elga Fabia
authors.initials: EF
authors.lastname: Belligni
authors.affiliation: Adult Autism Center, ASL TO2, Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Keller
authors.affiliation: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
authors.forename: Evelise
authors.initials: E
authors.lastname: Riberi
authors.affiliation: Department of Neuropsychiatry, University of Torino, Torino, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Gandione
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Calcia
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mancini
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giorgio
authors.affiliation: Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.|Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cavalieri
authors.affiliation: Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pappi
authors.affiliation: Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Talarico
authors.affiliation: Department of Surgical Sciences, University of Torino, Torino, Italy.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Fea
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Rubeis
authors.affiliation: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Cirillo Silengo
authors.affiliation: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ferrero
authors.affiliation: Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.|Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brusco
mesh_terms: D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics*
keywords: autistic spectrum disorder; contiguous gene syndrome; intellectual disability; obesity; schizophrenia