CHRNA7 triplication associated with cognitive impairment and neuropsychiatric phenotypes in a three-generation pedigree.
Eur J Hum Genet
; 22(9): 1071-6, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24424125
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linhagem
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Deficiências do Desenvolvimento
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Variações do Número de Cópias de DNA
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Receptor Nicotínico de Acetilcolina alfa7
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Deficiência Intelectual
Tipo de estudo:
Diagnostic_studies
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Risk_factors_studies
Limite:
Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article