How tiny DNA switch changes cause limb birth differences
Decoding the Mechanism of Pathogenic Enhancer Mutations In Congenital Limb Disorders
['FUNDING_R01'] · UNIVERSITY OF CALIFORNIA-IRVINE · NIH-11312709
Researchers are looking at how rare changes in DNA 'switches' turn on an important gene in the wrong place during limb development, which can cause extra fingers or toes and related developmental problems.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF CALIFORNIA-IRVINE (nih funded) |
| Locations | 1 site (IRVINE, UNITED STATES) |
| Trial ID | NIH-11312709 on ClinicalTrials.gov |
What this research studies
If your child has a limb birth difference, this project uses mouse models that carry the same rare DNA 'switch' changes seen in people to see why the SHH gene is turned on in the wrong part of the developing limb. The team will use transgenic mouse assays, detailed genetic tests, and 3D mapping of DNA interactions to follow which proteins bind the enhancer and how the DNA folds during limb development. They will compare normal and mutant enhancers across development to trace the steps that lead to extra digits or other developmental effects. The overall aim is to link a single non-coding DNA change to the biological events that cause congenital limb malformations.
Who could benefit from this research
Good fit: People born with limb malformations (for example polydactyly) or those known to carry rare ZRS enhancer variants, and their families, would be the most relevant candidates for sample donation or future clinical follow-up.
Not a fit: Patients whose limb differences are due to non-genetic causes or to mutations in genes unrelated to the ZRS/SHH pathway may not directly benefit from these findings.
Why it matters
Potential benefit: If successful, this work could improve genetic diagnosis and counseling for families and point toward ways to prevent or reduce some congenital limb malformations in the future.
How similar studies have performed: Prior genetic and mouse studies have linked ZRS enhancer variants to extra digits and the team reports promising preliminary transgenic mouse data, but the detailed transcriptional mechanism has not yet been fully worked out.
Where this research is happening
IRVINE, UNITED STATES
- UNIVERSITY OF CALIFORNIA-IRVINE — IRVINE, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: KVON, EVGENY — UNIVERSITY OF CALIFORNIA-IRVINE
- Study coordinator: KVON, EVGENY
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Autistic Disorder