Format

Send to

Choose Destination
Nat Commun. 2019 Aug 6;10(1):3529. doi: 10.1038/s41467-019-11437-w.

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

Author information

1
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, 10461, NY, USA.
2
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, 10461, NY, USA.
3
Department of Cell Biology and Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, 10016, NY, USA.
4
Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, M46 1R8, ON, Canada.
5
Pediatric Neurology Clinic, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot, 76100, Israel.
6
Genetics Institute, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot, 76100, Israel.
7
Department of Pharmacology, New York University School of Medicine, New York, 10016, NY, USA.
8
Centre for Applied Genomics and McLaughlin Centre, Hospital for Sick Children and University of Toronto, Toronto, M56 0A4, ON, Canada.
9
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, 10461, NY, USA.
10
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, 10461, NY, USA. bryen.jordan@einstein.yu.edu.
11
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, 10461, NY, USA. bryen.jordan@einstein.yu.edu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center