# Identification of germline modifiers of Neurofibromatosis type 1 tumors

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $656,513

## Abstract

Abstract
 Neurofibromatosis type 1 (NF1) is a genetic disorder that occurs in about 1:3000 individuals. NF1 is caused
by inheritance or de novo mutation/loss of the NF1 gene. Individuals with NF1 are predisposed to numerous
manifestations, including the development of plexiform neurofibromas (PNF) and/or optic pathway glioma (OPG).
Unlike in more aggressive tumors, apart from changes at NF1, PNF cells do not show many recurrent somatic
changes; somatic changes in OPG are rare. Twin studies suggest that germline modifiers of NF1 disease exist,
but these remain largely unstudied. Because the identification of NF1 modifiers should enable risk stratification
and identification of targetable therapeutic pathways in individuals with NF1 we developed a multidisciplinary
team of geneticists, bioinformaticians, statisticians and animal (mouse and fish) modelers. Relying on close
collaboration among team members, we will continue identifying genes showing increased numbers of potentially
disruptive variants to study. In Aim 1, we will expand our number of individuals with PNF and/or OPG and test if
variants are associated with tumor number, tumor burden, or presence of OPG. In Aim 2, we will test candidates
in a well-characterized mouse model of plexiform neurofibroma, using the power of mouse genetics. To enhance
rapid screening of relevant genes and variants we generated a zebrafish model of PNF and OPG, which will be
exploited in Aim 3, by screening for effects of larger numbers of genes predicted to act as NF1 modifiers. The
proposed research will provide a basis for precision medicine in NF1. If risk variants in genes are associated
with disease severity and/or correlate with tumor burden, then the development of genomic risk assessment
tools will be possible at diagnosis.

## Key facts

- **NIH application ID:** 10874120
- **Project number:** 1R01NS133200-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** NANCY RATNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $656,513
- **Award type:** 1
- **Project period:** 2024-09-10 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874120

## Citation

> US National Institutes of Health, RePORTER application 10874120, Identification of germline modifiers of Neurofibromatosis type 1 tumors (1R01NS133200-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10874120. Licensed CC0.

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