# Genetic Variants in Craniofacial Dystonias

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $589,767

## Abstract

Project Summary/Abstract
Among the many causes of craniofacial disease are focal dystonias such as blepharospasm (BSP) and
oromandibular dystonia (OMD), affecting the eyes and jaw, respectively, as well as Meige Syndrome, which
combines features of both. Dystonia is the contraction of agonist and antagonist muscles, that result in abnormal
postures and movement of the affected body parts. Craniofacial dystonias are poorly understood and have
limited treatment options. The proposed research is relevant to public health because understanding the causes
of dystonia, that interferes with vision and communication, will help to point the way toward the development of
new treatment.
We hypothesize that craniofacial dystonia (CFD) may be caused by both rare and common genetic variants. To
identify monogenic variants, we will perform whole exome sequencing of multiplex families with CFD. To assess
the contribution of common variants to CFD, we will use genome-wide association data to compute polygenic
risk scores and then correlate these with disease-related imaging signatures derived from CFD patients to
identify gene networks that may be driving the altered brain connectivity. To probe the functional effects of
identified mutations, we will knock them into iPSC lines using genome editing tools and analyze their localizations
and protein:protein interactions in neural cells as initial readouts of their pathogenic potential. These analyses
will establish a cellular platform which we will also use for characterizing new craniofacial disease variants
identified by our combined genetics and imaging analyses.

## Key facts

- **NIH application ID:** 10850593
- **Project number:** 5R01DE030464-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** NUTAN SHARMA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $589,767
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850593

## Citation

> US National Institutes of Health, RePORTER application 10850593, Genetic Variants in Craniofacial Dystonias (5R01DE030464-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10850593. Licensed CC0.

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