Indian Researchers Identify First Case of Novel USP18 Gene Mutation

In a significant advancement for genetic research, a team of Indian scientists has identified a novel mutation in the USP18 gene, marking the first documented case of its kind in the country. This discovery relates to recurrent neurological deterioration in children and provides new insights into Pseudo-TORCH syndrome type 2, an extremely rare inherited brain disorder previously recorded in only 11 cases globally.

The study, conducted by a multidisciplinary team from the Indira Gandhi Institute of Child Health (IGICH) in Bengaluru, in collaboration with Ramjas College (University of Delhi) and Redcliffe Labs, was published in the journal Clinical Dysmorphology. The researchers identified a previously unreported variant, c.358C>T (p.Pro120Ser), which impairs the USP18 gene’s function in regulating the body’s immune response.

Pseudo-TORCH syndrome type 2 results in severe neurological symptoms that mimic congenital infections without the involvement of any actual pathogens. When the USP18 gene malfunctions, it causes the immune system to become hyperactive, leading to unintended damage to the brain. This can result in seizures, developmental delays, and episodes of febrile encephalopathy.

Breakthrough in Diagnosis and Treatment

Dr. Vykuntaraju K. Gowda, a leading researcher at IGICH, described the discovery as a landmark moment for clinical diagnosis and treatment. He stated, “Identifying this novel mutation has completely changed the child’s diagnostic journey. It allows us to avoid unnecessary treatments, provide targeted care, and offer meaningful genetic counselling to the family.”

The research initiative was prompted by the case of an 11-year-old girl who had experienced neurological episodes since infancy. Her symptoms included recurring fever-related unconsciousness, seizures, and progressive calcium deposits in the brain. After numerous inconclusive evaluations, advanced exome sequencing alongside mitochondrial genome testing uncovered the novel USP18 mutation, finally offering clarity for her condition.

Dr. Himani Pandey, another member of the research team, emphasized the significance of this finding. She noted that this represents the first documented instance of a USP18-related disease manifesting with repeated febrile encephalopathy. This discovery underscores the transformative potential of early genetic testing in children presenting with unexplained neurological symptoms.

The implications of this research extend beyond a single case. It paves the way for more precise diagnoses, tailored treatment strategies, and informed family counselling for similar rare disorders. Researchers believe that increased awareness and understanding of USP18 mutations can significantly improve clinical outcomes for affected children.

As the scientific community continues to explore the complexities of genetic disorders, this novel discovery serves as a vital reminder of the importance of rigorous research and collaboration in advancing medical knowledge and patient care.