# Genetic modifiers of Duchenne Muscular Dystrophy

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $904,269

## Abstract

Project Summary
Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder that affects
approximately 1:3500 to 1:5200 live male births caused by mutations in the X-linked DMD
gene. DMD gene mutations result in absence of the dystrophin protein in muscle fibers,
leading to myofiber necrosis, endomysial fibrosis, and fat replacement. It is a devastating
disorder, leading to loss of ambulation by age 12, and historically to death by age 20. The
psychological and socioeconomic effects on families are enormous; these include but are
not limited to the costs of medical care, opportunity costs for career and work, and the
psychological toll taken on parents and siblings. Our long-term goal is to understand which
genes modify disease progression and severity of DMD. Confirming a hypothesis derived
from a genetic modifier of muscular dystrophies in mice, we have recently used data from
patients enrolled in the United Dystrophinopathy Project (UDP) to demonstrate that
polymorphisms in the LTBP4 gene influence age at loss of ambulation. Our objective in
this project is to identify additional genetic modifiers of skeletal muscle, cardiac, and
ventilatory function, and our central hypothesis is that such modifiers can be identified
by use of the UDP database, a unique resource that contains detailed phenotypic data
and archived DNA samples from over 900 DMD patients. Our specific aims are to 1)
update and analyze phenotypic data within the UDP cohort, 2) map modifier traits by high-
density single nucleotide polymorphism arrays, and 3) validate newly identified putative
genetic modifiers. Validation will engage collaborating networks of investigators in the US
and Europe, who have additional natural history cohorts of DMD patients. At the
conclusion of these Aims, we will have gained new information about modifier genes
associated with the severity and progression of DMD.

## Key facts

- **NIH application ID:** 10914841
- **Project number:** 5R01NS085238-08
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** KEVIN M FLANIGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $904,269
- **Award type:** 5
- **Project period:** 2014-05-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914841

## Citation

> US National Institutes of Health, RePORTER application 10914841, Genetic modifiers of Duchenne Muscular Dystrophy (5R01NS085238-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10914841. Licensed CC0.

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