title: The human clinical phenotypes of altered CHRNA7 copy number.
abstract: Copy number variants (CNVs) have been implicated in multiple neuropsychiatric conditions, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability (ID). Chromosome 15q13 is a hotspot for such CNVs due to the presence of low copy repeat (LCR) elements, which facilitate non-allelic homologous recombination (NAHR). Several of these CNVs have been overrepresented in individuals with neuropsychiatric disorders; yet variable expressivity and incomplete penetrance are commonly seen. Dosage sensitivity of the CHRNA7 gene, which encodes for the α7 nicotinic acetylcholine receptor in the human brain, has been proposed to have a major contribution to the observed cognitive and behavioral phenotypes, as it represents the smallest region of overlap to all the 15q13.3 deletions and duplications. Individuals with zero to four copies of CHRNA7 have been reported in the literature, and represent a range of clinical severity, with deletions causing generally more severe and more highly penetrant phenotypes. Potential mechanisms to account for the variable expressivity within each group of 15q13.3 CNVs will be discussed.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Madelyn A
authors.initials: MA
authors.lastname: Gillentine
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, United States. Electronic address: Schaaf@bcm.edu.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D017353:Gene Deletion; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: CHRNA7; Copy number variation; Neuropsychiatric disease; Nicotinic acetylcholine receptors