Scientists Discover Rare Genetic Disorder Affecting Brain Development

Researchers identify a new congenital disorder of glycosylation that disrupts normal protein function.

Apr. 14, 2026 at 5:48am

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An abstract, highly structured painting in soft, earthy tones of green, blue, and ochre, depicting sweeping geometric arcs, concentric circular forms, and precise botanical spirals, conceptually representing the intricate cellular processes and structural disruption involved in a newly discovered genetic disorder affecting brain development.A conceptual visualization of the complex glycosylation process and the structural disruption caused by a rare genetic mutation, shedding light on the underlying mechanisms of a newly discovered neurological disorder.Boston Today

Scientists at Sanford Burnham Prebys Medical Discovery Institute and an international team used genetic sequencing to discover a new rare genetic disease that impacts brain growth and development. The researchers found a mutation in the RPN1 gene, which carries the blueprint for the ribophorin I protein, an essential component of the cellular machinery responsible for glycosylation - the process of attaching sugar molecules to proteins. This structural defect leads to a reduction in proper protein glycosylation, causing a range of neurodevelopmental and other developmental issues.

Why it matters

The discovery of this new congenital disorder of glycosylation, now termed RPN1-CDG, expands the understanding of the genetic causes behind rare neurological diseases. A better grasp of how disruptions to the glycosylation process can impact normal cellular function and development will help provide more definitive diagnoses for patients suffering from unexplained neurodevelopmental disorders.

The details

The research team began by sequencing the genomes of two siblings with an unfamiliar neurodevelopmental disorder. They found a mutation in the RPN1 gene that was shared by the affected siblings but not their three unaffected siblings. This genetic error had not been previously reported. Further testing confirmed that the mutation led to instability in the ribophorin I protein, a key component of the oligosaccharyltransferase (OST) complex responsible for attaching sugar molecules to newly formed proteins. This structural defect caused a reduction in proper glycosylation of many proteins, leading to the range of developmental issues observed in the patients.

  • The findings were published on April 3, 2026 in the journal Human Genetics and Genomics Advances.

The players

Sanford Burnham Prebys Medical Discovery Institute

A non-profit medical research institute focused on discovering the fundamental molecular causes of disease and developing innovative therapies.

Hudson Freeze, PhD

The William W. Ruch Distinguished Endowed Chair and director of the Sanford Children's Health Research Center at Sanford Burnham Prebys.

Bobby G. Ng, PhD

A staff scientist in the Freeze lab at Sanford Burnham Prebys and the first author of the study.

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What they’re saying

“The glycosylation results from these tests reflected patterns we know well from other CDGs.”

— Hudson Freeze, Director, Sanford Children's Health Research Center

“Because the OST complex plays a role in every developmental process, that is why we see a range of neurodevelopmental and other developmental issues in CDGs.”

— Hudson Freeze, Director, Sanford Children's Health Research Center

What’s next

The researchers plan to continue studying this new congenital disorder of glycosylation, known as RPN1-CDG, to better understand the underlying mechanisms and explore potential treatment approaches.

The takeaway

The discovery of this rare genetic disease expands scientific knowledge about the complex role glycosylation plays in normal cellular function and development. Identifying the genetic causes behind unexplained neurological disorders is a critical step towards providing more definitive diagnoses and potential therapies for patients suffering from these debilitating conditions.