# METABOLIC CHANGES UNDERLYING 16P11.2 DELETION SYNDROME

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2020 · $243,444

## Abstract

Project Summary
Our proposal is based on the hypothesis that altered metabolism is associated with 16p11.2 deletion
syndrome (16pdel). We are taking a novel approach to define symptoms and treatment pathways for this
severe and prevalent mental health/neurodevelopmental syndrome, affecting 1:2000 people. Deletion of one
chromosomal interval, that includes 25 genes, is tightly associated with autism, intellectual disability, seizures,
hyperactivity, large body size and movement disorders. All evidence points to each symptom resulting from
interaction of two or more 16p11.2 genes. Strikingly, 8/25 genes in the interval encode enzymes or enzyme
modulators, and our data indicates a key three-way interaction between the 16p11.2 enzymes FAM57B, a
ceramide synthase; CDIPT, the only phosphatidylinositol synthase and ALDOA, a glycolytic enzyme. fam57b is
a pivotal `hub' gene, as it interacts with multiple 16p11.2 homologs in the accessible whole animal zebrafish
model. Encouraging preliminary data determined by metabolite profiling implicate lipid disruption as an
important component to 16pdel syndrome. There are three Aims, each based on preliminary data that will be
addressed in human neurons, including neurons derived from 16pdel syndrome iPS cells, with whole animal
tests in the zebrafish. The first Aim will determine changes in metabolism of human neurons and zebrafish
brain, mutant for 16p11.2 enzymes. The second aim will determine cellular and behavioral phenotypes in
affected human neurons and zebrafish mutants. The third aim will assess pharmacological modulation of
mutant phenotypes. This high reward proposal will identify erroneous biochemistry that contributes to the
disorder and provide an avenue for therapeutic intervention by rescuing implicated biochemical pathways.

## Key facts

- **NIH application ID:** 10294775
- **Project number:** 7R01MH119173-02
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Hazel L Sive
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,444
- **Award type:** 7
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294775

## Citation

> US National Institutes of Health, RePORTER application 10294775, METABOLIC CHANGES UNDERLYING 16P11.2 DELETION SYNDROME (7R01MH119173-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10294775. Licensed CC0.

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