# Role of POU4F1 in a Novel Form of Ataxia

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $244,453

## Abstract

PROJECT SUMMARY/ABSTRACT
Heterozygous, pathogenic variants in POU4F1 were recently reported by our group to cause a novel ataxia
syndrome (Webb et al., 2021). This neurological disorder is characterized by childhood onset ataxia, intention
tremor, and hypotonia, and affected individuals have global developmental delay with mildly impaired
intellectual development and speech delay or learning difficulties. POU4F1, also known as BRN3A, encodes a
class IV POU-domain containing transcription factor expressed in the developing and adult brain. Little is
known about the role POU4F1 plays in neurogenesis, neuronal differentiation, and neuronal survival in human
neurons. Therefore, we propose to use iPSC to generate cellular models of the human brain to interrogate the
consequences of POU4F1 haploinsufficiency. Our specific aims in this proposal are to 1) determine
transcriptional signatures, epigenetic status, and functional abnormalities resulting from POU4F1
haploinsufficiency in iPSC – derived neurons; 2) assess the impact of POU4F1 haploinsufficiency in a iPSC
model of the developing brain using cortical organoids; and 3) create a patient registry for POU4F1-related
ataxia and better define the clinical features of this newly identified disorder. Taken together, these studies will
uncover the pathophysiology, disease mechanism, and clinical spectrum of disease of POU4F1-related ataxia
and address fundamental questions of human neurodevelopmental biology.

## Key facts

- **NIH application ID:** 10878883
- **Project number:** 5R21NS130319-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Samuele G. Marro
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $244,453
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878883

## Citation

> US National Institutes of Health, RePORTER application 10878883, Role of POU4F1 in a Novel Form of Ataxia (5R21NS130319-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10878883. Licensed CC0.

---

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