title: CHRNA7 triplication associated with cognitive impairment and neuropsychiatric phenotypes in a three-generation pedigree.
abstract: Although deletions of CHRNA7 have been associated with intellectual disability (ID), seizures and neuropsychiatric phenotypes, the pathogenicity of CHRNA7 duplications has been uncertain. We present the first report of CHRNA7 triplication. Three generations of a family affected with various neuropsychiatric phenotypes, including anxiety, bipolar disorder, developmental delay and ID, were studied with array comparative genomic hybridization (aCGH). High-resolution aCGH revealed a 650-kb triplication at chromosome 15q13.3 encompassing the CHRNA7 gene, which encodes the alpha7 subunit of the neuronal nicotinic acetylcholine receptor. A small duplication precedes the triplication at the proximal breakpoint junction, and analysis of the breakpoint indicates that the triplicated segment is in an inverted orientation with respect to the duplication. CHRNA7 triplication appears to occur by a replication-based mechanism that produces inverted triplications embedded within duplications. Co-segregation of the CHRNA7 triplication with neuropsychiatric and cognitive phenotypes provides further evidence for dosage sensitivity of CHRNA7.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Soler-Alfonso
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Brazil.
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Carvalho
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Roney
authors.affiliation: Parkview Health Laboratories, Genetics Center, Fort Wayne, IN, USA.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Bader
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Katarzyna E
authors.initials: KE
authors.lastname: Kolodziejska
authors.affiliation: Parkview Health Laboratories, Genetics Center, Fort Wayne, IN, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Miller
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D000328:Adult; D002648:Child; D056905:Chromosome Breakpoints; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor