Researchers have previously linked TREX1 gene mutations to the development of a rare inherited small vessel disease called retinal vasculopathy with cerebral leukoencephalopathy (RVCL). What researchers didn’t know was why these genetic mutations caused progressive DNA damage. Until now.

An article covering the collaborative research into TREX1 mutations and RVCL describes how the research team came to their conclusion. The team, which consisted of members from the University of Pennsylvania’s Perelman School of Medicine and Niigata University’s Brain Research Institute, began by studying this rare disease in both human and animal cells. More specifically, the team utilized cells from mice and Drosophilia (small fruit flies). Researchers led with the hypothesis that TREX1 mutations lead to cellular instability.

In findings published in Nature Communications, the research team shares that:

• TREX1 mutations increase susceptibility to chemotherapy-related damage. As many individuals with RVCL are initially misdiagnosed with conditions like lupus or oncological malignancies, chemotherapy could worsen damage within their bodies and significantly advance disease progression.
• When both DNA strands break, the body usually implements a DNA repair process. However, in RVCL, the TREX1 mutations inhibited that process. Instead of being repaired, the DNA is deleted. Cells stop dividing like they should, which causes further damage and premature cellular aging. The researchers believe this information could be used to study premature cellular aging in other diseases as well, or to just look at DNA damage and its relationship to aging overall.
• There is a potential genetic similarity, or at least a genetic vulnerability, between TREX1, BRCA1, and BRCA2. The latter two genes are associated with breast cancer. Researchers believe TREX1 mutations could similarly increase breast cancer risk.

About Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL)

Also known as: Cerebroretinal vasculopathy; TREX1 vasculopathy; Hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS)

Retinal vasculopathy with cerebral leukodystrophy is a rare genetic disorder that affects highly vascularized tissue in the body. It causes small blood vessels to deteriorate and die, leading to visual changes and mini strokes. Symptoms of RVCL typically manifest between someone’s 30s and 50s. Unfortunately, this disease comes with a shorter lifespan. People typically live between 5-20 years following symptom onset. There are no curative or preventative treatments, which is why research is so important.

When symptoms of RVCL do appear, these may include:

• Floaters or blind spots in your field of vision
• Memory loss
• Progressive vision loss
• Mini strokes
• Tumor-like lesions on the brain
• Migraine
• Anemia (low red blood cell count)
• Hypothyroidism
• Osteonecrosis
• High blood pressure
• Liver and kidney disease