# Delineation of the natural history of Ollier disease and Muffucci syndrome and investigation of their genetic bases

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $550,444

## Abstract

PROJECT SUMMARY/ABSTRACT
Ollier disease (OD) and Maffucci syndrome (MS) are untreatable, poorly characterized, newly recognized cancer
susceptibility syndromes. Their genetic bases and pathways responsible for the formation and progression of
benign and malignant tumors are not known. Our long-term goal is to identify pharmacological approaches to
treat bone deformities and malignant transformation in patients with OD and MS and to prevent/treat related non-
syndromic forms of cancers associated with these conditions. Our central hypothesis in this application is that
OD and MS are distinct under-characterized cancer susceptibility syndromes caused by variants in multiple
genes that disrupt the HIF-1 pathway. The rationale for our project is that phenotypic characterization and
identification of the genetic causes of OD and MS have the potential to offer a strong scientific framework
whereby new pharmacological strategies to cancer therapy in these patients and patients with the non-syndromic
forms of the same cancers, such as chondrosarcomas and gliomas, can be developed. The central hypothesis
will be tested by pursuing three specific aims: 1) Comprehensively define the phenotypic features of patients
with OD and MS; 2) Discover the causative genes and variants of OD and MS in previously uncharacterized
cases; 3) Determine the effect of causative variants of OD or MS in the HIF-1 pathway. We will pursue these
aims using an innovative combination of genomic and functional techniques applied to a unique set of deeply
phenotyped patients. The proposed research is significant because it will: 1) Define the natural history of novel
cancer susceptibility syndromes; 2) Establish a unique OD and MS germline and tumor sample collection for
research use; 3) Identify the genetic bases of untreatable cancers, and; 4) Determine the role of the HIF-1
pathway in OD and MS. Our expected outcomes are to define the responsible variants and genes that cause
benign and malignant tumor formation in OD and MS and to fully elucidate the phenotypic features and natural
history of these disorders. Our results will have an important positive impact providing new opportunities for the
development of novel pharmacological therapies to treat patients with these diseases as well as those with
related non-syndromic forms of cancers such as of chondrosarcomas and gliomas.

## Key facts

- **NIH application ID:** 10766822
- **Project number:** 5U01HD107957-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CATHERINE M. GORDON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $550,444
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766822

## Citation

> US National Institutes of Health, RePORTER application 10766822, Delineation of the natural history of Ollier disease and Muffucci syndrome and investigation of their genetic bases (5U01HD107957-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10766822. Licensed CC0.

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