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A clinical research team from the LKS Faculty of Medicine, the University of Hong Kong (HKUMed), in collaboration with international genetic researchers, has led a groundbreaking study using multi-omics analysis to identify a novel gene, DDX39B, associated with a rare neurodevelopmental syndrome.
Genetic mutations in DDX39B impact brain function, resulting in developmental delay and hypotonia (diminished muscle tone), which are hallmark symptoms of this rare disorder. Following the identification of this gene, the research team discovered that DDX39B variants are linked to six known cases worldwide.
This research highlights the transformative potential of advanced multi-omics technology in decoding the genetic basis of rare diseases. The study’s findings, published in the journal Brain, significantly contribute to improved diagnostics, prevention strategies, and treatment options for rare disorders.
Significance of the Research
Dr. Brian Chung Hon-yin, Clinical Associate Professor in the Department of Pediatrics and Adolescent Medicine at HKUMed, spearheaded this investigation. His team specializes in rare disease research, previously estimating that approximately 1 in 67 individuals in Hong Kong—around 1.5% of the population—are affected by such conditions.
The research also underscores the substantial socio-economic burden of rare diseases, with each patient in Hong Kong incurring an estimated annual cost of HK$490,000. Additionally, individuals with rare diseases and their caregivers report a significantly lower health-related quality of life compared to the general population and those with other chronic illnesses.
Dr. Chung emphasized that early genetic diagnosis is essential in reducing both disease-related costs and financial distress. As a Commissioner for The Lancet Commission on Rare Diseases, he and his team advocate for greater global awareness and prioritization of rare disease research.
Case Study and Experimental Findings
In 2022, the HKUMed team investigated a local toddler who exhibited hypotonia from birth, leading to feeding difficulties. As the child grew, motor and speech delays became evident, but the underlying cause remained elusive.
Using advanced multi-omics technologies—including RNA sequencing (RNA-seq) and proteomics—the researchers analyzed the patient’s genetic profile and detected abnormal RNA splicing patterns, confirming that DDX39B mutations contribute to this syndrome. Further experimentation on zebrafish models revealed that DDX39B deletion led to symptoms such as reduced head size and short body length, mirroring those seen in human patients.
Dr. Chung described the findings as a major breakthrough, stating, “This is the first-ever identification of this neurodevelopmental syndrome. Many patients have lived without a diagnosis for years—this discovery provides clarity and relief to affected families. Understanding the genetic cause is a vital step toward precision medicine, where tailored treatment and support can be provided.”
The Future of Rare Disease Treatment
Multi-omics technology integrates genomics, epigenomics, transcriptomics, proteomics, and metabolomics, enabling a more comprehensive understanding of human diseases. This approach is proving instrumental in developing novel screening, diagnostic, preventive, and therapeutic strategies.
Dr. Chung and his team plan to expand their research by investigating additional genes related to the transcription-export (TREX) complex. Their goal is to uncover broader mechanisms underlying neurodevelopmental disorders and refine diagnostic and treatment strategies.
“We have established an international research consortium to further explore genetic mechanisms affecting neurodevelopment. By pooling global expertise, we hope to enhance diagnostic precision and develop targeted therapies to improve patient outcomes worldwide,” Dr. Chung explained.
The study represents a significant step forward in rare disease research, offering hope to patients and their families while paving the way for more advanced clinical interventions.
More information: Kevin T A Booth et al, ‘De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome,’ Brain (2025). DOI: 10.1093/brain/awaf035.
Journal information: Brain.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Readers should consult healthcare professionals for medical guidance regarding genetic conditions and treatment options.
