Daijiworld Media Network - New Delhi
New Delhi, Nov 27: In a major scientific breakthrough, Indian researchers have identified a novel mutation in the USP18 gene linked to recurrent neurological deterioration in children — marking the first such case reported from India. The discovery sheds new light on Pseudo-TORCH syndrome type 2, an extremely rare inherited brain disorder previously documented in only 11 cases worldwide.
The study was conducted by a multidisciplinary team from the Indira Gandhi Institute of Child Health (IGICH), Bengaluru, in collaboration with Ramjas College (University of Delhi) and Redcliffe Labs. Their findings, published in Clinical Dysmorphology, reveal a previously unreported variant — c.358C>T (p.Pro120Ser) — that disrupts the USP18 gene’s ability to regulate the body’s immune response.
Pseudo-TORCH syndrome type 2 causes severe neurological symptoms similar to congenital infections, but without any actual pathogen involvement. When the USP18 gene malfunctions, the immune system becomes hyperactive and inadvertently damages the brain, leading to seizures, developmental delays, and episodes of febrile encephalopathy.
Dr Vykuntaraju K. Gowda of IGICH said the discovery is a landmark moment for clinical diagnosis and treatment:
“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 was sparked by the case of an 11-year-old girl who had suffered neurological episodes since infancy, including recurring fever-related unconsciousness, seizures, and progressive calcium deposits in the brain. After years of inconclusive evaluations, exome sequencing combined with mitochondrial genome testing revealed the novel USP18 mutation — finally providing clarity.
Dr Himani Pandey, part of the research team, noted that this is the first documented instance of USP18-related disease presenting with repeated febrile encephalopathy.
The discovery highlights the transformative potential of early genetic testing in children with unexplained neurological symptoms, paving the way for more precise diagnosis, tailored treatment strategies, and informed family counselling in similar rare disorders.