New Genetic Disease Linked to Premature Aging and Cognitive Decline Discovered
Scientists have identified a rare genetic disorder that causes premature aging and significant cognitive impairment, differentiating it from previously known progeria syndromes. The discovery, made by researchers at Sanford Burnham Prebys Medical Discovery Institute and an international team, marks the first known project combining genome sequencing with cellular reprogramming to pinpoint the causative gene mutation and understand its effects.
The findings, published on March 19, 2026, in Nature Communications, shed light on a previously unknown disease affecting teenagers who exhibit symptoms of premature aging, such as whitening hair, alongside progressive loss of motor skills, neurological deficits, and intellectual decline. Unlike typical progeria conditions where cognitive function is often preserved, this new disease significantly impacts brain function.
Identifying the Culprit Gene: IVNS1ABP
Through genome sequencing and mapping of recessive traits, the research team traced the disease to a mutation in the IVNS1ABP gene. This gene provides instructions for building IVNS1ABP, a protein associated with influenza virus non-structural protein-1 binding. Notably, little prior research existed on this gene and its connection to aging or neurological conditions.
“Relatively little research has been done on this gene and protein, and no one has ever linked them to the biology of aging, premature aging diseases or neuropathy,” said Fang Yuan, PhD, staff scientist at Sanford Burnham Prebys and first author of the study.
Cellular Senescence and Disrupted Cell Division
To investigate the effects of the IVNS1ABP mutation, researchers reprogrammed skin cells from affected patients into induced pluripotent stem cells, then guided them to become neural progenitor cells. These cells, carrying the patient’s mutation, exhibited slower growth compared to healthy control cells.
This sluggish growth indicated cellular senescence – a state where cells stop dividing but don’t die, often triggered by DNA damage. Further analysis revealed three indicators of genome injury and increased expression of CDKN2A, a gene linked to cellular senescence. The team found that DNA damage occurred during cell division, potentially leading to cell death.
Actin Dynamics and the Root of the Problem
The researchers hypothesized that the mutated gene disrupted cell division by interacting with other proteins. Their experiments identified 14 potential interacting proteins, ten of which are connected to actin – a key structural component of cells.
“During cell division, the actin filament needs to form an anchoring structure, and it usually forms a very round and even ring structure,” explained senior and corresponding author Su-Chun Zhang, MD, PhD, the Jeanne and Gary Herberger Leadership Chair in Neuroscience and the director of and professor in the Center for Neurologic Diseases at Sanford Burnham Prebys. “But in the mutant cells, the altered actin forms a shrunken and irregularly shaped ring, so cells are not pulled apart in a symmetrical way and suffer damage.”
The mutation appears to disrupt the precise coordination of actin dynamics, hindering proper cell division. Experiments showed that stabilizing the actin structure with specific chemicals improved cell division rates in the mutant cells.
Future Directions and Potential Treatments
This research underscores the power of combining cellular reprogramming and patient-derived stem cell models to study rare and poorly understood diseases. The team is currently developing an animal model to further investigate the disease and test potential therapies. Initial cellular studies suggest that correcting steps in the molecular processes could potentially reverse some of the observed defects.
“It will be important to complement these findings with studies in an animal model we’re developing, but what we’ve done already demonstrates that this approach is a powerful tool for defining new diseases and developing potential treatments,” said Zhang.