Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome

Abigail U. Carbonell, Chang Hoon Cho, Jaafar O. Tindi, Pamela A. Counts, Juliana C. Bates, Hediye Erdjument-Bromage, Svetlana Cvejic, Alana Iaboni, Ifat Kvint, Jenny Rosensaft, Ehud Banne, Evdokia Anagnostou, Thomas A. Neubert, Stephen W. Scherer, Sophie Molholm, Bryen A. Jordan

Research output: Contribution to journalArticle

Abstract

Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.

Original languageEnglish (US)
Article number3529
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Haploinsufficiency
Gene encoding
genes
coding
disorders
etiology
proteins
Autistic Disorder
phenotype
Genes
Proteins
Phenotype
Induced Pluripotent Stem Cells
Inborn Genetic Diseases
Attention Deficit Disorder with Hyperactivity
synapses
Stem cells
Proteomics
Synapses
stem cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Carbonell, A. U., Cho, C. H., Tindi, J. O., Counts, P. A., Bates, J. C., Erdjument-Bromage, H., ... Jordan, B. A. (2019). Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. Nature Communications, 10(1), [3529]. https://doi.org/10.1038/s41467-019-11437-w

Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. / Carbonell, Abigail U.; Cho, Chang Hoon; Tindi, Jaafar O.; Counts, Pamela A.; Bates, Juliana C.; Erdjument-Bromage, Hediye; Cvejic, Svetlana; Iaboni, Alana; Kvint, Ifat; Rosensaft, Jenny; Banne, Ehud; Anagnostou, Evdokia; Neubert, Thomas A.; Scherer, Stephen W.; Molholm, Sophie; Jordan, Bryen A.

In: Nature Communications, Vol. 10, No. 1, 3529, 01.12.2019.

Research output: Contribution to journalArticle

Carbonell, AU, Cho, CH, Tindi, JO, Counts, PA, Bates, JC, Erdjument-Bromage, H, Cvejic, S, Iaboni, A, Kvint, I, Rosensaft, J, Banne, E, Anagnostou, E, Neubert, TA, Scherer, SW, Molholm, S & Jordan, BA 2019, 'Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome', Nature Communications, vol. 10, no. 1, 3529. https://doi.org/10.1038/s41467-019-11437-w
Carbonell AU, Cho CH, Tindi JO, Counts PA, Bates JC, Erdjument-Bromage H et al. Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. Nature Communications. 2019 Dec 1;10(1). 3529. https://doi.org/10.1038/s41467-019-11437-w
Carbonell, Abigail U. ; Cho, Chang Hoon ; Tindi, Jaafar O. ; Counts, Pamela A. ; Bates, Juliana C. ; Erdjument-Bromage, Hediye ; Cvejic, Svetlana ; Iaboni, Alana ; Kvint, Ifat ; Rosensaft, Jenny ; Banne, Ehud ; Anagnostou, Evdokia ; Neubert, Thomas A. ; Scherer, Stephen W. ; Molholm, Sophie ; Jordan, Bryen A. / Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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