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Indian researchers identify novel USP18 gene mutation tied to rare childhood neurological disorder

The breakthrough came during the evaluation of an 11-year-old girl who has endured severe neurological symptoms since infancy, including recurrent fever-associated unconsciousness, persistent seizures, developmental delays, and progressive brain calcification. Despite extensive testing over the years, clinicians were unable to identify an infectious cause, even though the symptoms closely mimicked congenital infections.

• By Newsdesk
• New Delhi
• Nov 29, 2025

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In a significant scientific breakthrough, Redcliffe Labs has identified a previously unreported mutation in the USP18 gene, India’s first documented discovery of its kind offering critical insights into an exceptionally rare pediatric neurological disorder.

The newly discovered variant, c.358C>T (p.Pro120Ser), has been linked to Pseudo-TORCH syndrome type 2, a hereditary condition so uncommon that only a few cases have been recorded worldwide. The breakthrough came during the evaluation of an 11-year-old girl who has endured severe neurological symptoms since infancy, including recurrent fever-associated unconsciousness, persistent seizures, developmental delays, and progressive brain calcification. Despite extensive testing over the years, clinicians were unable to identify an infectious cause, even though the symptoms closely mimicked congenital infections.

To solve this long-standing clinical puzzle, Redcliffe Labs, working alongside specialists at the Indira Gandhi Institute of Child Health in Bengaluru, conducted advanced exome and mitochondrial genome sequencing. The analysis pinpointed the USP18 mutation as the underlying cause of the child’s recurrent neurological decline.

USP18 is a key immune regulator, responsible for keeping type I interferon signalling in balance. The newly identified mutation appears to impair the protein’s function, removing an essential regulatory control and triggering excessive immune activity. This chronic inflammatory response likely led to repeated episodes of brain injury and neurological deterioration observed in the child.

Reflecting on the discovery, Redcliffe Labs Founder and CEO Aditya Kandoi said:
“This breakthrough is more than a scientific milestone; it shows how advanced genomics and expert clinical interpretation can reshape a child’s life trajectory. Identifying a novel USP18 variant reflects our commitment to pushing the boundaries of precision medicine and strengthens India’s leadership in genomic innovation.”

Lead genomic scientist Himani Pandey noted that this is the first documented instance of a USP18-related disorder presenting as recurrent febrile encephalopathy, adding an important new dimension to the clinical understanding of this rare condition.

By documenting this mutation, researchers hope to support early diagnosis and improved clinical management for similar cases worldwide. The findings reinforce the importance of genomic testing in children with unexplained neurological symptoms helping prevent misdiagnoses, reduce unnecessary treatments, and guide more precise, informed care for affected families.