Researchers identify a new recessive neurodevelopmental disorder using data from the National Genomic Research Library
Multiple research groups have identified a new recessive neurodevelopmental disorder which is believed to be one of the most common genetic causes of severe childhood epilepsy. The pieces of research, published in Nature Genetics, used data from Genomics England’s National Genomic Research Library (NGRL) to make the discovery.
The studies offer long-awaited answers for families who may have spent years searching for a diagnosis and show how national genomic datasets are transforming understanding of rare and complex conditions.
The condition, called Recessive RNU2–2-related neurodevelopmental disorder, is associated with early-onset epilepsy and developmental delay. While symptoms vary considerably depending on the child’s specific genetic changes, common features include low muscle tone and limited speech. Some children also develop movement disorders and can have trouble walking.
The condition’s cause
RNU2‑2–related neurodevelopmental disorder is caused by changes in a small noncoding gene called RNU2-2. More specifically, an almost complete absence of a molecule called U2-2 RNA, which is produced by the RNU2-2 gene. Non-coding genes are DNA sequences that do not provide instructions for making proteins.
Children with the condition typically inherit one altered copy of the gene from each parent, although sometimes changes arise spontaneously. While the parents are unaffected, the combined effect of both copies of the gene in their children leads to disrupted brain development in their child.
NGRL data accelerating discovery
To make the discovery, the separate research teams from Manchester University NHS Foundation Trust and The University of Manchester and the Icahn School of Medicine at Mount Sinai examined changes in thousands of genes from Genomics England’s NGRL.
The NGRL is one of the world’s largest and most valuable databases of its kind. Its growth to date has benefitted NHS patients and participants, as well as others affected by rare conditions and cancers around the world, by uncovering new diagnoses and driving the development of innovative treatments.
“This discovery, made possible through Genomics England’s National Genomic Research Library, will provide much sought-after answers to families who will likely have spent years searching for a diagnosis. It shows why genomic data at national scale can be so valuable to researchers in helping them make what can be life-changing breakthroughs for patients, and why genomics is becoming an increasingly key focus for healthcare systems around the world.
“A diagnosis means families can access support and find a community which we know can be incredibly significant for them, alongside sometimes having new information around any other complications associated with the condition either now or in the future. It may even be the first step towards potential treatments through future research.
“This news is a powerful example of how research linked to clinical care, powered by genomic data from patients and participants in the UK, can change lives around the world.”
Dr Rich Scott
Chief Executive Officer of Genomics England
Professor Siddharth Banka, senior author of the study from the University of Manchester, said the discovery “shines a light on areas of the human genome that have been under‑explored for far too long.”
Dr. Ernest Turro, senior author of the study from the Icahn School of Medicine, said the discovery “will enable tens of thousands of families affected by this previously hidden genetic condition to receive closure through a genetic diagnosis.”
The study builds on previous research in the field. Namely:
- In a related gene, RNU4-2, linked to a neurodevelopmental condition known as ReNU syndrome that was also discovered in 2024 through access to data in the NGRL
- Additional research in the RNU2-2 gene, again through NGRL data
Genomics England continue to work with NHS clinical teams, researchers and academic partners to enable discoveries like this - helping to advance understanding of complex genetic conditions and improve outcomes for patients and families.
A step forward for families seeking answers
For families like Ava Begley’s, who spent years searching for a diagnosis, this breakthrough brings clarity after a long period of uncertainty.
Ava’s dad, Daniel, and mum, Elizabeth, said: “Ava is a beautiful little girl with a bright presence. She loves looking through books, music, sensory play, being outdoors, and spending time with her family. Even with the immense challenges she faces, Ava brings extraordinary love and meaning into our lives. She has a deep presence about her that touches everyone who meets her.
“For many years we have been through extensive medical investigations, specialist appointments, and genetic testing, hoping to find an answer that could explain Ava’s condition and guide her care. Like many rare disease families, we have lived with a long period of uncertainty.
“Having a diagnosis is incredibly meaningful. It gives Ava a name and a place in the medical world, rather than being an unanswered mystery. It helps us feel that we are getting closer to the starting point of being able to find a cure or treatment and provides hope that research and awareness may lead to better understanding and support in the future."
Genomics England thanks the patients and participants who consented to donate their data to the NGRL and who made this research and its findings possible.
