Jessica Margrill, ReNU Syndrome United
For 13 years, Jessica searched for answers for her son. A diagnosis of RNU4-2 Syndrome finally provided those answers and opened the door to a community of families facing similar experiences. Hear Jessica share her family’s diagnostic odyssey and the importance of genome sequencing and reanalysis for families still searching for answers.
Dr Nicky Whiffin breaks down the science behind ReNU syndrome
Follow the journey behind the discovery of ReNU syndrome. Researchers explain how they identified the condition and helped families around the world receive a diagnosis, while a family shares the impact of finally having answers and connecting with others with similar experiences.
Find out more about ReNU syndrome: https://rnuuk.org/
n-Lorem 2026 Nano-rare Patient Colloquium Poster Session
Wei Zhang, Ph.D. Associate Director, ASO Core Research, n-Lorem
Small non-coding RNAs are emerging as an important yet largely untapped class of disease-causing therapeutic targets. In this poster, we will describe how at n-Lorem, we have established an integrated discovery strategy to enable precision antisense oligonucleotide (ASO) therapeutics against pathogenic small RNAs, including spliceosomal small nuclear RNAs (snRNAs). Using RNU4-2 as a prototype, we combined mechanistic disease characterization, allele-selective ASO discovery, structural RNA analysis, endogenous RNA modification mapping, patient-derived cellular models, and functional splicing rescue to identify potent therapeutic candidates. This work demonstrated that mutant RNU4-2 acts through a toxic gain-of-function mechanism and that allele-selective ASOs can restore normal splicing in patient-derived cells. Beyond RNU4-2, this discovery pipeline establishes a broadly applicable strategy for targeting emerging small non-coding RNA disorders, creating new therapeutic opportunities for a rapidly expanding class of genetic diseases.
Kelly Cervantes is the bestselling author of The Luckiest and Normal Broken, host of CURE Epilepsy’s Seizing Life podcast, and creator of the blog Inchstones. In this conversation, she shares her views about seizures and reflects on life with her medically complex daughter, Adelaide, who died in 2019. Kelly speaks candidly about caregiving, grief, joy, and holding all three at once.
One proposed mechanism for ReNU syndrome is disrupted pre-mRNA splicing within the spliceosome. This video illustrates that theory by showing how pathogenic RNU4-2 variants may alter spliceosome function, leading to errors in RNA processing and, ultimately, disease. While this is one hypothesis supported by current research, the full disease mechanism is still being investigated.
Geo explains the benefits of using Citizen Health
Nicky Whiffin explains how our genes function and how changes in those genes can lead to rare conditions such as ReNU Syndrome.
Human DNA contains tens of thousands of genes, many of which provide instructions for making proteins—the essential “workhorses” that enable cells to function properly. These instructions are carried out through a process where DNA is transcribed into messenger RNA (mRNA), which is then translated into proteins.
When a gene is altered, the resulting protein may not function as expected. In ReNU Syndrome, these genetic changes disrupt normal protein activity, which can interfere with critical developmental pathways—particularly those involved in brain development and cellular regulation. This disruption can lead to a range of neurological and developmental features observed in affected individuals.
To better understand these effects, researchers used CRISPR gene-editing technology to introduce specific genetic variants into cellular or model systems. This allowed scientists to replicate the exact mutation seen in individuals with ReNU Syndrome and directly observe how it alters protein function and downstream biological processes. By comparing normal and edited systems, researchers are identifing the mechanisms driving the condition.
Over 300 million people worldwide live with a rare disorder, yet fewer than half receive a genetic diagnosis and over 95% lack disease-specific treatments. Current diagnostic approaches focus largely on protein-coding regions, missing important variants in non-coding exonic regions such as untranslated regions and non-coding RNAs. Studying these regions can uncover new diagnoses, reveal disease mechanisms, and accelerate the development of targeted therapies.
n-Lorem 2025 Nano-rare Patient Colloquium Poster Session
Wei Zhang, Ph.D., MPA Associate Director of Core Research
Mutations in U-rich RNAs are increasingly recognized as drivers of NDDs. Although their short length and structured nature presents challenges, ASO technology offers a unique therapeutic opportunity. This work focuses on a recently identified mutation in RNU4-2, highlighting its functional characterization and n-Lorem’s therapeutic strategy to address toxic effects.
Sizzle reel by Dr. John Rinn, a world-leading expert in long noncoding RNAs
We’re launching Blue4ReNU! Doing something with the color blue, donate & post a video asking others to do the same!
“I’m going #Blue4ReNU in support of (name/those with ReNU Syndrome).
Tagging [4 people]! Show your blue in the next 24 hours!
Donate any combination of 4s & 2s to support the RNU4-2/ReNU Crew!
Add the hashtags and the donation link below. Thank you!”
#blue4renu #renusyndrome #renusyndromeunited #renuhope #donateandnominate
Nicola Whiffin presents "Interpreting variation in small nuclear RNAs in neurodevelopmental disorders" at the 2025 Mutational Scanning Symposium
🚀 New Episode Alert – RareMind: Podcast on Genomics & AI
🎙️ Episode 3 is live now: ReNU Syndrome – RNU4-2 Mutations and Neurodevelopmental Disorders
🧬 In this episode, we explore how RNU4-2, a non-coding RNA gene integral to the major spliceosome, has been identified as the cause of ReNU Syndrome, a newly recognized neurodevelopmental disorder.
🧠 Recent studies uncovered rare de novo variants clustered in an 18-base pair region of RNU4-2, associated with a consistent clinical phenotype: intellectual disability, microcephaly, short stature, and motor delay. These variants disrupt splicing fidelity and highlight the role of non-coding RNAs in the pathogenesis of rare disease.
🔬 This episode reveals how the search beyond protein-coding regions is reshaping our understanding of spliceosomal disorders and driving forward rare disease diagnostics.
🎧 Tune in now and be part of the growing movement transforming RNA biology into clinical insight.
#Genomics #RareDisease #RNA #Neurodevelopment #Spliceosome #ReNU #NonCodingRNA #Podcast #RareMind
Recorded at St Anne's College, University of Oxford on 29th April 2025.
This event brought together key people involved in the discovery of ReNU syndrome, a condition affecting development and learning which was first identified last year yet potentially impacts tens of thousands of families across the world.
Hearing from experts involved in the discovery, this event reflected on the importance of genomic diagnosis for rare conditions and the factors necessary both to identify new conditions, and to learn about what they might mean for patients and families.
The focus of the evening was around the discovery process and the broader implications of receiving a genetic diagnosis, rather than specific practical implications of a ReNU syndrome diagnosis. Where speakers give permission, talks will be available on our website shortly after the event.
Now that we have a diagnosis, what’s next? One of the most critical steps is to gather data to learn more about ReNU syndrome, so that we can apply these learnings towards treatment options. We’re using the Rare-X Data Collection Program to power the research forward.
Standardized genome sequencing and phenotyping of large patient cohorts provide an opportunity for discovering the unknown etiologies. Here we demonstrate our computational approach to rare disease association analysis on the 100,000 Genomes Project dataset, comprising building a compact database, the "Rareservoir", containing rare variant genotypes and phenotypes, and applying our rare disease association method "BeviMed"…
28 February 2026
Rare diseases affect 1 in 12 Canadians: Toronto family shares diagnosis experience