Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility

Elena Bacchelli, Agatino Battaglia, Cinzia Cameli, Silvia Lomartire, Raffaella Tancredi, Susanne Thomson, James S. Sutcliffe, Elena Maestrini

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Chromosome 15q13.3 recurrent microdeletions are causally associated with a wide range of phenotypes, including autism spectrum disorder (ASD), seizures, intellectual disability, and other psychiatric conditions. Whether the reciprocal microduplication is pathogenic is less certain. CHRNA7, encoding for the alpha7 subunit of the neuronal nicotinic acetylcholine receptor, is considered the likely culprit gene in mediating neurological phenotypes in 15q13.3 deletion cases. To assess if CHRNA7 rare variants confer risk to ASD, we performed copy number variant analysis and Sanger sequencing of the CHRNA7 coding sequence in a sample of 135 ASD cases. Sequence variation in this gene remains largely unexplored, given the existence of a fusion gene, CHRFAM7A, which includes a nearly identical partial duplication of CHRNA7. Hence, attempts to sequence coding exons must distinguish between CHRNA7 and CHRFAM7A, making next-generation sequencing approaches unreliable for this purpose. A CHRNA7 microduplication was detected in a patient with autism and moderate cognitive impairment; while no rare damaging variants were identified in the coding region, we detected rare variants in the promoter region, previously described to functionally reduce transcription. This study represents the first sequence variant analysis of CHRNA7 in a sample of idiopathic autism.

Original languageEnglish
Pages (from-to)715-723
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Autistic Disorder
Phenotype
Gene Fusion
Nicotinic Receptors
Genetic Promoter Regions
Intellectual Disability
Genes
Sequence Analysis
Psychiatry
Exons
Seizures
Chromosomes
Autism Spectrum Disorder
Cognitive Dysfunction
Chromosome 15q13.3 Microdeletion Syndrome

Keywords

  • 15q13.3
  • Copy number variants
  • Neurodevelopmental disorders
  • Sequence variants

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Bacchelli, E., Battaglia, A., Cameli, C., Lomartire, S., Tancredi, R., Thomson, S., ... Maestrini, E. (2015). Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. American Journal of Medical Genetics, Part A, 167(4), 715-723. https://doi.org/10.1002/ajmg.a.36847

Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. / Bacchelli, Elena; Battaglia, Agatino; Cameli, Cinzia; Lomartire, Silvia; Tancredi, Raffaella; Thomson, Susanne; Sutcliffe, James S.; Maestrini, Elena.

In: American Journal of Medical Genetics, Part A, Vol. 167, No. 4, 01.04.2015, p. 715-723.

Research output: Contribution to journalArticle

Bacchelli, E, Battaglia, A, Cameli, C, Lomartire, S, Tancredi, R, Thomson, S, Sutcliffe, JS & Maestrini, E 2015, 'Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility', American Journal of Medical Genetics, Part A, vol. 167, no. 4, pp. 715-723. https://doi.org/10.1002/ajmg.a.36847
Bacchelli, Elena ; Battaglia, Agatino ; Cameli, Cinzia ; Lomartire, Silvia ; Tancredi, Raffaella ; Thomson, Susanne ; Sutcliffe, James S. ; Maestrini, Elena. / Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. In: American Journal of Medical Genetics, Part A. 2015 ; Vol. 167, No. 4. pp. 715-723.
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