# Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder

> **NIH NIH P50** · UNIVERSITY OF WASHINGTON · 2024 · $250,806

## Abstract

Project Summary – Research Project 
The mechanisms underlying Intellectual and Developmental Disabilities (IDDs) remain largely 
unknown. A substantial number of individuals with IDDs have developmental brain 
malformations which are associated with considerable morbidity and mortality. This proposal 
focuses on a newly identified IDD condition (MCTT syndrome), characterized by IDD, epilepsy, 
characteristic craniofacial differences, and two important brain malformations: polymicrogyria 
(PMG) and rhombencephalosynapsis (RES). PMG is a common feature in many IDDs and is 
strongly associated with developmental disability and epilepsy. Although PMG is known to be 
due to aberrant neuronal migration, the causes and molecular mechanisms remain incompletely 
understood, and few good animal models exist. RES is a unique cerebellar malformation 
characterized by fusion of the cerebellar hemispheres with partial or complete absence of a 
recognizable cerebellar vermis; almost nothing is known about the causes and mechanisms 
underlying RES, and no animal models exist. This project represents a synergistic collaboration 
between human and mouse model-focused investigators with support from three IDDRC Cores 
(Genetics, Brain Imaging, and Animal Behavior). At the completion of this project, we will 
understand the effects of C-terminal truncating MN1 variants on gene regulation and brain 
development. Our specific aims are: 1. To dissect the role of MN1 in transcriptional regulation 
using stem cell derived models; 2. To dissect the developmental mechanisms underlying MN1- 
related PMG and RES in mice.

## Key facts

- **NIH application ID:** 10907628
- **Project number:** 5P50HD103524-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** DANIEL DOHERTY
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,806
- **Award type:** 5
- **Project period:** 2020-07-28 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907628

## Citation

> US National Institutes of Health, RePORTER application 10907628, Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder (5P50HD103524-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10907628. Licensed CC0.

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