The Sunday Times announced Dr Nicky Whiffin, 2024 Lister Prize Fellow, among its Alternative Honours List 2025 for her role in uncovering ReNU syndrome—a previously unexplained neurodevelopmental disorder. Her team’s discovery, forged through large-scale data science and close collaboration with clinicians and families, is already changing how diagnoses are made and pointing to future therapies.
We recently discovered a genetic basis for ReNU syndrome… I’m hoping to use some of the Prize money to investigate whether we can develop therapies for people with ReNU Syndrome.
Finding answers in the ‘dark genome’
Most clinical genomics for neurodevelopmental disorders still focus on the small portion of the genome that encodes proteins. This leaves many patients and their families without firm diagnoses or really understanding of the mechanisms behind rarer, de novo genetic conditions that can arise spontaneously or are associated with non-coding genomic sequences.
Nicky’s group interrogates non-coding regions, including untranslated regions (UTRs) and small nuclear RNAs, that often regulate and fine-tune how genes are expressed and translated.
“Some genetic conditions can be due to genetic changes that are inherited from a parent,” Nicky explains in blog post about her research in 2024, “but a lot of what we look at are severe developmental disorders that are caused by genetic changes that have newly arisen in a child and aren’t present in either of their parents. We call these de novo variants. These changes often arise from replication errors in sperm or egg cells in the parents which are then passed on. So they’re not inherited diseases, but they are genetic. Often the condition is so severe that the child won’t go on to have a family, but if they were to have a child of their own, in theory it could be passed on.”
A global collaboration led by Nicky’s team showed that variants in expressed but untranslated RNA from the RNU4-2 non-coding region (U4 snRNA) cause a neurodevelopmental syndrome now known as ReNU syndrome. Nicky’s team estimated that RNU4-2 variants account for around 0.4% of all neurodevelopmental disease cases worldwide.
After finding the initial statistical signal, the team pursued saturation genome editing across RNU4-2 to test hundreds of possible variants. These studies clarifed which changes were damaging and even revealed distinct dominant and recessive mechanisms associated with the same gene, providing an experimental benchmark that accelerates clinical classification. Early analyses identified 115 affected individuals, of whom around three-quarters carried a dinstinct single base insertion.
Nicky was able to show that the RNU4-2 variants disrupted splicing, consistent with the known role of this non-coding region during spliceosome activation and providing some mechanistic explanation for the clinical features of the syndrome.
From national data to real-world diagnosis
One of our main goals is to create tools that enable us to better translate our science into clinical settings.
ReNU is one of the first snRNA-mediated neurodevelopmental disorders to be recognised at scale. It was uncovered in collaboration with the Genomics England’s National Genomic Research Library and the 100,000 Genomes Project, demonstrating the power of linking rigorous analytics to national datasets. The genetic discoveries have already informed diagnoses for several children in the UK, providing long-awaited answers to families and, crucially, the impetus to create a community for support and advocacy.
The translation of Nicky’s research into clinical diagnostics is happening at pace, but clinical application of research often faces signficant barriers. In 2022, Nicky convened and worked with a panel of clinical and research scientists working in the field of variants within non-coding regions to explore ways to unlock research insights for diagnostics and new treatments. The panellists co-developed a set of recommendations to increase the number and range of non-coding region variants that can be clinically interpreted. “Together with a compatible phenotype,” the authors wrote, “[this] can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.”
Celebrated by the Sunday Times
We are delighted to see The Sunday Times feature Nicky in its roll call of alternative honours for 2025, a list that celebrates “those whose good deeds in the past 12 months have either gone unnoticed or deserve a bit more celebration.” Nicky sits alongside Wicked’s Cynthia Erivo, Alan Carr and a host of non-celebrities who have achieved extraordinarily brave, intrepid and charitable acts.
“It was a dream to me,” Nicky told the newspaper. “I spent all my career wanting to make a difference… We don’t want patients to be forgotten.”
Further reading
- Their children have a rare condition. They didn’t know its name – until now (Washington Post, 2025)
- My son Charlie – and the breakthrough that changed our lives (The Sunday Times, 2025)
- Whiffin research group website
