# Understanding the effect of Hao-Fountain syndrome-causing mutations on neuronal development

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2024 · $461,528

## Abstract

ABSTRACT
Hao-Fountain syndrome is a newly identified rare pediatric neurodevelopmental disorder caused by deletions
and mutations of the USP7 gene. The molecular mechanisms and pathophysiology of the disease remain poorly
understood, preventing the development of potential treatments for Hao-Fountain patients. USP7 is a
deubiquitinating enzyme implicated in the maintenance of protein homeostasis, stem cell identity, self-renewal,
and control of dendritic branching in primary neurons. A model system has not yet been created but is
indispensable for understanding the disease and for the evaluation of potential personalized therapies for Hao-
Fountain Syndrome. In this proposal, we will create the first human-based cellular model of Hao-Fountain to test
the effect of disease-linked mutations on the enzymatic function of USP7 (Aim 1), and on neuron differentiation
potential and morphology (Aim 2). The patient-derived induced pluripotent stem cells will be differentiated into
cortical neurons to create the Hao-Fountain model system that will be shared with the greater community to
accelerate the understanding of this newly discovered and devastating disease.

## Key facts

- **NIH application ID:** 10987390
- **Project number:** 1R21NS135343-01A1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Irina Bezsonova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $461,528
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987390

## Citation

> US National Institutes of Health, RePORTER application 10987390, Understanding the effect of Hao-Fountain syndrome-causing mutations on neuronal development (1R21NS135343-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987390. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*