title: The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications.
abstract: Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals.
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Moursund Street, Ste. 1325, Houston, TX, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Gillentine
authors.affiliation: Autism Center, Texas Children's Hospital, Houston, TX, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: L N
authors.initials: LN
authors.lastname: Berry
authors.affiliation: Autism Center, Texas Children's Hospital, Houston, TX, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Goin-Kochel
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Moursund Street, Ste. 1325, Houston, TX, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ali
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ge
authors.affiliation: Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Guffey
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: V
authors.initials: V
authors.lastname: Hannig
authors.affiliation: Northeast Indiana Genetics, Fort Wayne, IN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.|Department of Neurology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Proud
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shinawi
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Medical Genetics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lin
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Lalani
authors.affiliation: Medical Genetics, Shodair Children's Hospital, Helena, MT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Department of Pediatrics-Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Child Health, Division of Genetics and Metabolism, Phoenix Children's Hospital, University of Arizona College of Medicine, Phoenix, AZ, USA.
authors.forename: T
authors.initials: T
authors.lastname: Grebe
authors.affiliation: Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Minard
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. schaaf@bcm.edu.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Moursund Street, Ste. 1325, Houston, TX, USA. schaaf@bcm.edu.
authors.forename: C P
authors.identifier: 0000-0002-2148-7490
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D010375:Pedigree; D010641:Phenotype; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: 15q13.3 microduplication; Autism spectrum disorder; Behavior; CHRNA7; Neurodevelopment