Redcliffe Labs reports India’s first USP18 gene mutation tied to rare pseudo-TORCH disorder

New Delhi: Redcliffe Labs, a leading pan-India diagnostics organization, has reported a significant scientific discovery: the identification of a rare USP18 gene mutation linked to recurrent neurological decline in children.

The research, published in Clinical Dysmorphology, documents a previously unreported variant, c.358C>T (p.Pro120Ser), expands clinical understanding of Pseudo-TORCH syndrome type 2, a condition often challenging to diagnose due to overlapping symptoms with infectious and metabolic disorders.

The clinical evaluation and long-term management of the child were guided by the diagnostic insights from Dr. Himani Pandey, Lab Head, Genomics at Redcliffe Labs, in collaboration with Dr. Vykuntaraju K. Gowda, Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru.

The findings come from the case of an 11-year-old girl who began experiencing symptoms from infancy, including repeated episodes of febrile encephalopathy, that is, fever-linked unconsciousness, seizures, delayed development, and a small head size. Over the years, her scans also showed increasing calcium deposits in different parts of the brain. With only 11 cases reported worldwide, this study adds a meaningful contribution to global medical knowledge. To understand the underlying cause of these recurring neurological problems, advanced genetic testing was recommended. Through a focused DNA test called exome sequencing with mitochondrial genome sequencing, the team was able to identify a previously unknown change in the USP18 gene, offering clarity after years of uncertainty.

Pseudo-TORCH syndrome type 2 is a very rare inherited condition that affects how a child’s brain grows and functions. Children with this disorder often show severe neurological symptoms that resemble congenital infections, but without any actual infection. The USP18 gene usually helps regulate the body’s immune response, preventing excessive inflammation. When this gene does not work correctly, the body’s defense system becomes overactive and begins to harm the brain.

The newly identified mutation alters the structure of the USP18 protein, weakening its ability to control inflammation. This overactive immune response can explain the child’s repeated episodes of fever-triggered neurological decline. Understanding this connection is essential because it helps doctors recognize early warning signs, avoid unnecessary treatments for infections, and focus instead on monitoring and managing conditions linked to immune overactivation.

Aditya Kandoi, Founder and CEO, Redcliffe Labs, said, “We believe the future of diagnostics lies in uncovering answers that were once thought impossible. This breakthrough is more than a scientific milestone; it demonstrates how advanced genomics, when paired with deep clinical insight, can fundamentally change a child’s trajectory. Discovering a novel USP18 variant is not just an academic achievement; it reflects our commitment to pushing the boundaries of precision medicine in India. Complex neurological conditions often leave families navigating uncertainty for years, and breakthroughs like this help bring clarity where it matters most. I am proud of our team and our collaborators for setting a new benchmark in rare disease diagnostics. This is the kind of work that strengthens India’s leadership in genomic innovation and moves us closer to a future where no medical mystery remains unsolved.”

Commenting on the study, Dr Himani Pandey, Lab Head, Genomics, Redcliffe Labs, said, “We remain committed to expanding our specialized diagnostic capabilities to address some of the most challenging medical conditions seen in clinical practice. This case is also the first documented case of USP18-related disease presenting with recurrent febrile encephalopathy. The successful diagnosis reflects the depth of expertise our team brings through advanced tests such as exome sequencing. These capabilities enable us to solve complex and often long-standing medical mysteries. We applaud the research team’s achievement. This strengthens the role of Redcliffe Labs in advancing diagnostic precision and improving outcomes for patients with rare and difficult-to-diagnose conditions.”

This study adds valuable information to the small number of known cases worldwide and introduces a new genetic variant to medical literature. By confirming the diagnosis and understanding the child’s long-term illness pattern, the research helps guide future care for similar patients and supports families with clearer answers. The findings highlight the importance of early genetic testing in children with unexplained neurological symptoms and open the door for more targeted approaches to care in the future.