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

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2 Scopus citations


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
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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

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    Carbonell, A. U., Cho, C. H., Tindi, J. O., Counts, P. A., Bates, J. C., Erdjument-Bromage, H., Cvejic, S., Iaboni, A., Kvint, I., Rosensaft, J., Banne, E., Anagnostou, E., Neubert, T. A., Scherer, S. W., Molholm, S., & 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