# Epigenetic dysregulation of muscle differentiation in Kabuki syndrome

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $553,354

## Abstract

PROJECT SUMMARY
Kabuki Syndrome (KS) is a rare disease caused by heterozygous pathogenic mutations in two known
genes: KDM6A (~20% cases) and KMT2D (~80% cases). Both genes are broadly expressed in many
tissues and their activity spans temporally from development to postnatal adult life. KS patients present
with various degrees of clinical abnormalities, including severe muscular hypotonia and reduced muscle
strength. Whether hypotonia develops as a consequence of nerve conduction malfunction or it is due to a
cell-autonomous primary defect in skeletal muscle is currently unknown. Further, skeletal muscle tissue
from patients affected by KS has not been thoroughly studied. Our main hypothesis is that skeletal muscle
tissue is primarily affected by mutations in KMT2D, which results in dysregulated muscle function. We
propose to validate our hypothesis via the following specific Aims: 1) Define primary versus secondary
muscle function defects using constitutive and conditional mouse models of KS; 2) Determine the gene
networks and molecular targets of KMT2D driving muscle hypotonia in constitutive and conditional KS
mouse models; 3) Define muscle satellite cell heterogeneity and `immaturity' in conditional and constitutive
KS models, as well as in human patients. The work proposed will fill major gaps in our lack of knowledge
about etiology of hypotonia in Kabuki syndrome and will pave the way for clinical improvements of patient
care.

## Key facts

- **NIH application ID:** 10342143
- **Project number:** 1R01AR080079-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** EMANUELA GUSSONI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $553,354
- **Award type:** 1
- **Project period:** 2022-02-02 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10342143

## Citation

> US National Institutes of Health, RePORTER application 10342143, Epigenetic dysregulation of muscle differentiation in Kabuki syndrome (1R01AR080079-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10342143. Licensed CC0.

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