91直播

A 6-year-old girl is one of more than 80 people worldwide who has finally received a diagnosis of a new condition following a landmark breakthrough by scientists and doctors in 91直播.

Ava Begley鈥檚 parents say they feel 鈥渄eeply grateful鈥� that the researchers, from 91直播 University NHS Foundation Trust (MFT) and The University of Manchester (UoM), have made this discovery, which is one of the most common genetic causes of severe epilepsy.

Delivered through the this groundbreaking work is already transforming the lives for many children and young people around the world, providing long-awaited answers and hope for the future.

Ava鈥檚 parents, Daniel Begley and Elizabeth Dowd, from Sydney, Australia, said: 鈥淥ur first reaction was a mixture of emotion 鈥� relief at finally having a diagnosis, but also sadness in understanding the seriousness of the condition and how rare it is. Above all, we felt grateful that Ava鈥檚 experience may contribute to greater knowledge and future progress and treatment.鈥�

This new condition, which the researchers have named as 鈥淩ecessive RNU2-2-related neurodevelopmental disorder鈥�, results in difficult-to-control seizures and severe developmental delays in children, often appearing within their first year of life.

Published in the journal , the research has so far identified 84 individuals living with the new condition, while experts estimate that thousands more remain undiagnosed across the world.

The team estimates that millions of people globally could be 鈥榗arriers鈥� of the faulty gene behind this disorder.

91直播 lead and first author of the paper Dr Adam Jackson, Academic Clinical Fellow at the 91直播 Centre for Genomic Medicine, part of MFT, and The University of Manchester, explained: 鈥淲e believe that as many as in 1 in 100 people could unknowingly be carriers of this condition. If both parents are carriers, there is a 1 in 4 chance with every pregnancy that their child could be affected. We estimate roughly 1 in 40,000 people may be living with this condition, making it one of the most common neurodevelopmental disorders currently known. Our discovery brings hope for many patients and families who have been searching for answers and is already having a positive impact around the world.鈥�

This major advance builds on in which they showed the importance of the RNU genes in brain development and function.

The research team made the new discovery by analysing changes in several hundred RNU genes in data of individuals who took part in the 100,000 Genomes Project, a Genomics England initiative to sequence and study the role genes play in health and disease.

Dr Jackson, who is also an early career researcher in the NIHR 91直播 BRC鈥檚 Rare Conditions Theme, explained: 鈥淲hat makes this discovery even more remarkable is that RNU2-2 is extremely small in comparison to other genes. Unlike most other genes, RNU2-2 does not even make a protein. We were astonished to discover how changes in this tiny gene can have such profound effects in so many individuals.鈥�

Children with the condition experience severe early on in life, often in their first year. This means they have seizures 鈥� sudden surges of electrical activity in the brain which can cause the body to stiffen, jerk, shake and lose consciousness. These seizures can be difficult to fully control with medication, highlighting the urgent need for improved therapies.

The condition also has a profound impact on brain development, causing delays or inability to achieve key milestones such as walking or talking. Almost all affected individuals have significant learning problems.

Ava鈥檚 story

6-year-old Ava has lived with complex neurological symptoms from early childhood and requires full-time care and ongoing medical support.

Ava鈥檚 condition includes developmental delay, profound intellectual disability and severe epilepsy with frequent seizures. She would often experience 100 to 200 seizures per day, but these are now more controlled with medication.

Ava is non-verbal and cannot communicate through speech or gestures. She requires full-time support with daily life, including bathing, toileting and feeding. She also experiences major motor and balance difficulties, can only walk short distances and falls frequently. Ava often bites and pulls hair out and screams in frustration.

Collaborating with 91直播 researchers, the Sydney Children鈥檚 Hospital Clinical Genetics Team who support Ava and her family, were able to link Ava鈥檚 condition to the newly identified recessive RNU2-2-related disorder.

Ava鈥檚 dad, Daniel and mum, Elizabeth, said: 鈥淎va 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.

鈥淔or many years we have been through extensive medical investigations, specialist appointments, and genetic testing, hoping to find an answer that could explain Ava鈥檚 condition and guide her care. Like many rare disease families, we have lived with a long period of uncertainty.

鈥淗aving 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/treatment, and provides hope that research and awareness may lead to better understanding and support in the future.

鈥淲e believe that rare disease research is vital, not only for families like ours, but for the broader medical community. Ava鈥檚 journey has been challenging, but she is deeply loved, and we are committed to advocating for her and for all children living with rare and complex conditions.鈥�

91直播 lead and senior author Consultant Clinical Geneticist at the 91直播 Centre for Genomic Medicine at MFT, Professor of Genomic Medicine and Rare Diseases at UoM and Rare Conditions Theme Co-Lead at the NIHR 91直播 BRC said: 鈥淥ur work helps expand knowledge of conditions related to RNU genes, an emerging group of diseases which potentially affect around 1 in 10,000 individuals globally. It also shines a light on the regions of the human genome sometimes dismissed as 鈥榡unk DNA鈥�. We now see that so-called 鈥榙ark regions鈥� are vital for health.鈥�

Prof Banka, who is also Clinical Director of the , a virtual centre based at MFT which aims to improve the lives of people with rare conditions, added: 鈥淎t MFT, we have established a dedicated RNU clinic to identify and support more patients with these conditions. Looking to the future, this discovery paves the way to help unlock life-changing treatments for the recessive RNU2-2-related neurodevelopmental disorder.鈥�

Professor Marian Knight, Scientific Director for NIHR Infrastructure, said: 鈥淒iscovering the cause for conditions like Ava鈥檚 is the first step to personalised treatment and improved lifelong health and quality of life. This breakthrough is a testament to the robust research infrastructure the NIHR has developed over the last 20 years, enabling us to turn world-class genomic science into better care.鈥�

• The paper 'Biallelic variants in RNU2-2 cause a remarkably frequent developmental and epileptic encephalopathy is published in DOI: .