Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders

Catarina T. Correia, Inês C. Conceição, Bárbara Oliveira, Joana Coelho, Inês Sousa, Ana F. Sequeira, Joana Almeida, Cátia Café, Frederico Duque, Susana Mouga, Wendy Roberts, Kun Gao, Jennifer K. Lowe, Bhooma Thiruvahindrapuram, Susan Walker, Christian R. Marshall, Dalila Pinto, John Nurnberger, Stephen W. Scherer, Daniel H. GeschwindGuiomar Oliveira, Astrid M. Vicente

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. Methods. From the AGP CNV genomic screen in 2,147 ASD individuals, we selected for characterization an ANXA1 gene duplication that was absent in 4,964 population-based controls. We further screened the duplication in a follow-up sample including 1,496 patients and 410 controls, and evaluated clinical correlations and family segregation. Sequencing of exonic/downstream ANXA1 regions was performed in 490 ASD patients for identification of additional variants. Results: The ANXA1 duplication, overlapping the last four exons and 3'UTR region, had an overall prevalence of 11/3,643 (0.30%) in unrelated ASD patients but was not identified in 5,374 controls. Duplication carriers presented no distinctive clinical phenotype. Family analysis showed neuropsychiatric deficits and ASD traits in multiple relatives carrying the duplication, suggestive of a complex genetic inheritance. Sequencing of exonic regions and the 3'UTR identified 11 novel changes, but no obvious variants with clinical significance. Conclusions: We provide multilevel evidence for a role of ANXA1 in ASD etiology. Given its important role as mediator of glucocorticoid function in a wide variety of brain processes, including neuroprotection, apoptosis, and control of the neuroendocrine system, the results add ANXA1 to the growing list of rare candidate genetic etiological factors for ASD.

Original languageEnglish
Article number28
JournalMolecular Autism
Volume5
Issue number1
DOIs
StatePublished - Apr 10 2014

Fingerprint

Annexins
Annexin A1
Genes
Gene Duplication
3' Untranslated Regions
Genome
Autistic Disorder
Inheritance Patterns
Neurosecretory Systems
Population Control
Autism Spectrum Disorder
Glucocorticoids
Virulence
Exons
Apoptosis
Phenotype
Brain

Keywords

  • ANXA1
  • Autism
  • Brain homeostasis
  • Copy number variants
  • Duplication
  • Glucocorticoids

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental Neuroscience
  • Developmental Biology
  • Molecular Biology

Cite this

Correia, C. T., Conceição, I. C., Oliveira, B., Coelho, J., Sousa, I., Sequeira, A. F., ... Vicente, A. M. (2014). Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders. Molecular Autism, 5(1), [28]. https://doi.org/10.1186/2040-2392-5-28

Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders. / Correia, Catarina T.; Conceição, Inês C.; Oliveira, Bárbara; Coelho, Joana; Sousa, Inês; Sequeira, Ana F.; Almeida, Joana; Café, Cátia; Duque, Frederico; Mouga, Susana; Roberts, Wendy; Gao, Kun; Lowe, Jennifer K.; Thiruvahindrapuram, Bhooma; Walker, Susan; Marshall, Christian R.; Pinto, Dalila; Nurnberger, John; Scherer, Stephen W.; Geschwind, Daniel H.; Oliveira, Guiomar; Vicente, Astrid M.

In: Molecular Autism, Vol. 5, No. 1, 28, 10.04.2014.

Research output: Contribution to journalArticle

Correia, CT, Conceição, IC, Oliveira, B, Coelho, J, Sousa, I, Sequeira, AF, Almeida, J, Café, C, Duque, F, Mouga, S, Roberts, W, Gao, K, Lowe, JK, Thiruvahindrapuram, B, Walker, S, Marshall, CR, Pinto, D, Nurnberger, J, Scherer, SW, Geschwind, DH, Oliveira, G & Vicente, AM 2014, 'Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders', Molecular Autism, vol. 5, no. 1, 28. https://doi.org/10.1186/2040-2392-5-28
Correia CT, Conceição IC, Oliveira B, Coelho J, Sousa I, Sequeira AF et al. Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders. Molecular Autism. 2014 Apr 10;5(1). 28. https://doi.org/10.1186/2040-2392-5-28
Correia, Catarina T. ; Conceição, Inês C. ; Oliveira, Bárbara ; Coelho, Joana ; Sousa, Inês ; Sequeira, Ana F. ; Almeida, Joana ; Café, Cátia ; Duque, Frederico ; Mouga, Susana ; Roberts, Wendy ; Gao, Kun ; Lowe, Jennifer K. ; Thiruvahindrapuram, Bhooma ; Walker, Susan ; Marshall, Christian R. ; Pinto, Dalila ; Nurnberger, John ; Scherer, Stephen W. ; Geschwind, Daniel H. ; Oliveira, Guiomar ; Vicente, Astrid M. / Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders. In: Molecular Autism. 2014 ; Vol. 5, No. 1.
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AU - Conceição, Inês C.

AU - Oliveira, Bárbara

AU - Coelho, Joana

AU - Sousa, Inês

AU - Sequeira, Ana F.

AU - Almeida, Joana

AU - Café, Cátia

AU - Duque, Frederico

AU - Mouga, Susana

AU - Roberts, Wendy

AU - Gao, Kun

AU - Lowe, Jennifer K.

AU - Thiruvahindrapuram, Bhooma

AU - Walker, Susan

AU - Marshall, Christian R.

AU - Pinto, Dalila

AU - Nurnberger, John

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AU - Geschwind, Daniel H.

AU - Oliveira, Guiomar

AU - Vicente, Astrid M.

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