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Pittsburgh, PA – A groundbreaking discovery by geneticists at the University of Pittsburgh School of Public Health has revealed that a gene “silencer” residing in so-called “junk DNA” can prevent the onset of a devastating neurological disorder. This finding, published in Nature Communications, provides new insights into why some individuals with a genetic mutation linked to autosomal dominant leukodystrophy (ADLD) never develop symptoms.
ADLD is a fatal, adult-onset neurological disease affecting only a few thousand individuals worldwide. The disorder results from an extra copy of the lamin B1 gene, which triggers the degradation of myelin—the protective sheath surrounding nerves. Symptoms typically appear between the ages of 40 and 50 and include muscle weakness, seizures, and cognitive decline.
A Chance Conversation Sparks a Major Breakthrough
Senior author Dr. Quasar Padiath, M.B.B.S., Ph.D., professor and chair of Pitt Public Health’s Department of Human Genetics, has long studied ADLD and the role of lamin B1 in myelin loss. The breakthrough discovery occurred after a chance discussion with a neighboring geneticist whose collaborator had a patient with a lamin B1 duplication but no symptoms.
“Of all the 30,000 genes in the human genome, my colleague’s collaborator had a patient with a mutation in the exact gene I was researching,” Padiath said. “That patient started this entire study.”
Upon further investigation, Padiath and his team found two other families with the lamin B1 duplication who remained symptom-free. Using advanced genetic tools such as CRISPR gene editing, artificial intelligence-based computational models, and mouse studies, the researchers identified a silencing element in non-coding, or “junk,” DNA. This element interacts with lamin B1 and suppresses its activity—but only in oligodendrocytes, the brain cells responsible for producing myelin.
Implications for Diagnosis and Genetic Counseling
The study explains why lamin B1 overexpression causes disease in some individuals but not in others. It also suggests that genetic testing for ADLD should include screening for the silencer duplication, as patients who inherit both the gene duplication and the silencer are unlikely to develop the disorder.
“This discovery allows us to reassure some patients—who might have otherwise received a fatal prognosis—that they will not develop this cruel disease,” Padiath said. “It also helps us understand why a gene duplication affecting all cells in the body only manifests in one cell type.”
Beyond ADLD, this research has potential implications for other demyelinating disorders, such as multiple sclerosis. Padiath emphasized that the role of junk DNA in gene regulation is only beginning to be understood and could hold the key to future genetic therapies.
A Global Collaboration
The research involved scientists from institutions across the United States, the United Kingdom, Portugal, Brazil, Saudi Arabia, Canada, and Sweden. The full study is available in Nature Communications under the DOI: 10.1038/s41467-025-56378-9.
Disclaimer:
This article is for informational purposes only and does not constitute medical advice. Readers should consult healthcare professionals for guidance on genetic conditions and related concerns.
