From Genetic Puzzles to Precision Therapeutics
December 23, 2025 |
How was a new rare disease discovered through Singapore’s Undiagnosed Disease Program? And how will technology allow us to change how we discover rare diseases in the future? Read more to find out.
A/Prof Saumya Jamuar
Senior Consultant, Genetics service, KK Women’s and Children’s Hospital
Director, SingHealth Duke-NUS Institute of Precision Medicine
Lead Principal Investigator, Singapore Undiagnosed Disease Programme
S.Christy Rohani-Montez
Senior Director of Clinical Strategy
Rare Disease Education Lead
Medscape Education
Christy: I’m so excited to be in Singapore speaking with you Saumya, about Singapore’s Undiagnosed Disease Program.
Can you tell me first a little about yourself and how you got into rare diseases?
Saumya: Sure, so I’m a pediatrician and clinical geneticist at KK Women’s and Children’s Hospital. Since I was young, I’ve loved puzzles. To me, a patient with a rare disease is a puzzle with multiple pieces that need to be put together. I saw that as I was training in pediatrics where I would see patients being managed by the cardiologist, the neurologist, the gastroenterologist, and more. They would each be focusing on their specialty, and I found myself taking a step back and asking, “Hey, are these issues all connected in some way?”
That’s where I realized rare diseases play a part, because these rare diseases tend to connect the different organ systems and specialties. That passion for puzzle-solving got me into this field. What propelled it further was the pediatric setting, because the stakes are much higher for children. Once you get an answer and have that “aha” moment where it all makes sense, that brings so much joy into the work and accelerates the desire to continue.
Christy: Tell me about the condition named after you and the program behind it?
Saumya: I established Singapore’s undiagnosed disease program, which we call BRIDGES (Bridging Research Innovations for the Diagnosis of GEnetic Diseases in Singapore), to connect patients with genomic technologies. One of our first major successes came when 2 siblings were referred to my clinic with epilepsy and developmental delays where their speech was more affected than their motor skills. Standard tests were all negative, so we enrolled them in BRIDGES where we performed whole exome sequencing with our collaborators at A*STAR (Singapore’s Agency for Science, Technology and Research), and identified a novel variant in a gene called UGDH.
The product of UGDH is an enzyme that’s critical for building the structural matrix of the brain. You can imagine if the matrix isn’t there, the circuitry is missing. The brain is just a lot of wires, and if the wires aren’t connected properly, that’s when things go haywire. This led to the phenotype we were seeing: epilepsy and developmental delays. We reached out to our global network and found 18 other families with similar features and variants in the same gene. Through lab work with patient cells and cerebral organoids, we proved this was the cause and had discovered a new disease, which was named after me, the Jamuar Syndrome, and is also known as UGDH-related disorder.
Christy: What has the BRIDGES program achieved since then?
Saumya: We have successfully recruited over 850 families over the last decade, and have steadily improved our diagnostic yield from about 30% to 49%, comparable to international benchmarks. Beyond the diagnosis itself, the results have a profound impact. All families receive precise genetic counseling, and in 80% of cases, we can stop the “diagnostic odyssey” of endless tests.
Most importantly, in 27% of our diagnosed cases, there has been a direct impact on each patient’s medical management. For example, one child was hospitalized for her entire first year of life with multiple infections. An exome sequence revealed an immune dysregulation that could be treated with a bone marrow transplant. She finally went home. This was our first real foray into precision therapeutics, where knowing the exact genetic pathway allowed us to provide a targeted, life-changing treatment.
Christy: What are your long-term goals for the future?
Saumya: We are focused on 2 key areas. Firstly, we are expanding access to genomics to underserved regions in Southeast Asia through our Genomics for Kids in ASEAN initiative, generously supported by the Temasek Foundation.
Secondly, we are looking ahead to the next decade, which will be all about therapeutics. Today, only 5% of rare diseases are treatable. To change that, we are developing a therapeutic platform. Instead of a slow, single-gene, single-disease approach, we want to categorize conditions based on their functional outcome—for example, is the protein absent or is it dysfunctional? Then, we can match the problem to a class of solutions (like gene replacement or gene editing) and a delivery system that can target the affected organ. This creates a systematic, 3-dimentional matrix to treat many more patients at a much faster rate and probably at lower costs.
Christy: Your work is incredible, thanks so much for speaking with me today!
For more information, please contact Christy Rohani Montez PHD –
srohani@medscape.net
About Medscape Education
Medscape Education (medscape.org) is the leading destination for continuous professional development, consisting of more than 30 specialty-focused destinations offering thousands of free CME and CE courses for physicians, nurses, and other healthcare professional
This content was provided by Medscape Education
Company Details
Latest Content from Medscape Education
The Lasting Impact of Cytomegalovirus Education
Education on the signs, symptoms, and potential complications of cytomegalovirus (CMV) is in need of constant development, as this common disease affects nearly 1 in 3 children by age 5...
Medscape Education Publishes the Results of Multinational, Multispecialty Survey of Physicians on Rare Disease Educational Needs
Medscape Education has published the results of a global survey of its kind, assessing the educational needs of physicians on rare diseases. This survey of 978 clinicians worldwide across 16...
Medscape Showcases Outcomes in Austria for EASL Congress
Medscape recently attended the EASL Congress in Austria, where they successfully showcased the outcomes of their Wilson Disease education program. One of their achievements was presenting a poster on "Online...
Medscape is Bringing Outcomes to the #HomeOfNeurology
Budapest, Hungary is set to become Medscape's next destination as they gear up for the highly anticipated 9th Annual Congress of the European Academy of Neurology. As an integral part...
Medscape Education: ACOG 2023 Publication
Medscape Education is making a difference! We are wrapping CMV Awareness Month with a look at the impact of CMV education on OB/GYN learners. Take a look as Medscape Senior...
It’s the Era of Outcomes at ERA 2023
The Medscape team has bid farewell to the beautiful city of Milano, Italy and our European nephrology colleagues. The team was thrilled to meet up with so many ground-breaking clinicians,...
International NASH Day 2023
Shari Dermer, PhD of Medscape Education, hosted Michael Betel, Founder and President of Fatty Liver Alliance, in an engaging conversation around the importance of NASH awareness, diagnosis, and prognosis. Listen...
Shining a Spotlight on Patient Centricity in Frankfurt for EHA
The Medscape Oncology team has made their way back from Frankfurt, Germany after another successful EHA 2023 conference. While at the event, the team interacted with conference attendees at the...
Skylines and Oncology Headlines in Chicago for ASCO 2023
ASCO 2023 was a huge success for Medscape Oncology with connections made with members and conference attendees during the event at the Medscape Oncology booth on the exhibit floor and...
Medscape Oncology and American Society of Clinical Oncology Collaborate to Offer Cancer-Specific Training to Multidisciplinary Members of the Oncology Care Team
This week Medscape Oncology announced an exciting collaboration with ASCO® which you read on the Cision PR news wire here or below:The American Society of Clinical Oncology (ASCO®), a leader at...