How SEL1L-HRD1 protein changes can cause developmental and neurological problems
Mechanisms Underlying the Pathogenesis of SEL1L-HRD1 ERAD Disease Variants
This project looks at how changes in two proteins (SEL1L and HRD1) may lead to developmental delays, intellectual disability, and early-onset ataxia in affected children and families.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Virginia NIH-funded |
| Lab location | 1 site (Charlottesville, United States) |
| Project ID | NIH-11267223 on NIH RePORTER |
What this research studies
From a patient's view, the team is combining lab experiments and animal models with information from families who carry rare SEL1L or SYVN1 (HRD1) gene changes to understand why these changes cause brain and development problems. They use genetically modified mice and cellular studies to see how the mutant proteins affect protein handling in cells, and compare those findings with the genetic and clinical data from affected families in several countries. The researchers work with clinical geneticists in Saudi Arabia, France, and Italy who identified affected families, so human genetic information informs the lab work. The goal is to pin down the biological steps from the gene change to the symptoms so future tests or treatments can be developed.
Who could benefit from this research
Good fit: Ideal candidates are people or families with bi-allelic SEL1L or SYVN1 (HRD1) variants or children with early-onset cerebellar ataxia, global developmental delay, or severe intellectual disability who have had genetic testing.
Not a fit: People with unrelated causes of developmental delay or ataxia and those without SEL1L/SYVN1 gene changes are unlikely to benefit directly from this specific project.
Why it matters
Potential benefit: If successful, this work could improve diagnosis and genetic counseling for families and point toward targets for future therapies addressing the faulty protein pathway.
How similar studies have performed: Related animal studies and a dog model have linked SEL1L changes to ataxia and metabolic roles, but the human disease variants are newly identified and their mechanisms remain largely untested.
Where this research is happening
Charlottesville, United States
- University of Virginia — Charlottesville, United States (Active)
Researchers
- Principal investigator: Qi, Ling — University of Virginia
- Study coordinator: Qi, Ling
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.