Researchers in India have reported the first documented case in the country of a novel mutation in the USP18 gene, linked to a rare pediatric neurological disorder. The discovery, by Redcliffe Labs in collaboration with the Indira Gandhi Institute of Child Health (IGICH), Bengaluru, adds a new genetic variant to the global understanding of Pseudo‑TORCH syndrome type 2, an extremely uncommon inherited disorder.
The identified variant, described as c.358C>T (p.Pro120Ser), emerged from long-term study and genetic testing of an 11-year-old girl who had suffered recurrent fever-triggered unconsciousness, seizures, developmental delays and progressive brain calcifications since infancy.
The diagnosis was established through advanced exome sequencing combined with mitochondrial genome sequencing.
The novel mutation appears to impair the structure and function of the USP18 protein, which normally helps regulate immune response — preventing excessive activation. When this regulatory function is compromised, an over-active immune response can lead to inflammation and damage in the developing brain.
This mechanism helps explain why children with Pseudo-TORCH syndrome type 2 may show neurological decline similar to congenital infections, despite absence of any pathogen.
Because Pseudo-TORCH syndrome type 2 is exceedingly rare and closely mimics infectious or metabolic disorders, diagnosis has always been difficult. The discovery of this novel USP18 variant broadens the clinical spectrum of the disease and demonstrates the vital role of genetic sequencing in uncovering causes of unexplained neurological symptoms in children.
The researchers say this finding not only represents a milestone in rare-disease diagnostics in India but also contributes to international medical literature — offering clinicians clinical guidance to consider genetic testing when children present with recurrent encephalopathy, seizures, developmental delay or brain calcifications without a clear infectious cause.
This first report of a USP18 gene mutation in India may help pave the way for more precise diagnosis and better-informed management of rare neuro-immune disorders in children, while also highlighting the promise of precision medicine and genomics in tackling medical mysteries previously beyond reach.
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