Indian scientists identify rare gene mutation causing recurrent neurological disorders in children - Video

Indian scientists from Indira Gandhi Institute of Child Health, have uncovered a rare USP18 gene mutation causing repeated brain problems in kids, bringing India's first case of this ultra-rare disorder to light.

This breakthrough, published in Clinical Dysmorphology, spotlights Pseudo-TORCH syndrome type 2-a genetic condition mimicking brain infections but without germs. Previously known in just 11 cases worldwide, it now has an Indian footprint thanks to teams from Indira Gandhi Institute of Child Health, Ramjas College (Delhi University), and Redcliffe Labs.

Pseudo-TORCH syndrome type 2 tricks doctors because symptoms like seizures, developmental delays, small head size (microcephaly), and brain calcium buildup look like infections from birth. But it's genetic: the USP18 gene normally keeps the immune system in check to avoid over-inflammation. A faulty gene makes immunity hyperactive, attacking the brain during fevers and causing recurrent decline.

The discovery came from an 11-year-old girl with lifelong issues-fever-triggered unconsciousness (febrile encephalopathy), seizures, slow growth, and worsening brain scans showing calcium deposits. After years of mystery, doctors used exome sequencing (scanning most genes) plus mitochondrial DNA checks.

This revealed a new mutation: c.358C>T (p.Pro120Ser). Parents carried one faulty copy each (heterozygous), confirming inheritance. This change weakens the USP18 protein, unleashing uncontrolled inflammation.

This is the first USP18 case with repeated fever-brain attacks, expanding global knowledge. Early genetic tests like exome sequencing can now diagnose quickly, skip wrong infection treatments, and focus on immune control.

Experts like Dr. Vykuntaraju K. Gowda and Dr. Himani Pandey stress this advances precision medicine in India. It gives families answers, guides care, and pushes genomic testing for unexplained kid brain issues—potentially saving lives through targeted therapies.

REFERENCE: Gowda, Vykuntaraju K.a,*; Srinivasan, Varunvenkat M.b,*; Varghese, Archanaa; Kinhal, Uddhava V.a; Pandey, Himanic; Lal, Devid. USP18 gene mutation associated with recurrent encephalopathy, intracranial calcification, and microcephaly: case report, long-term follow-up, and literature review. Clinical Dysmorphology ():10.1097/MCD.0000000000000538, August 15, 2025. | DOI: 10.1097/MCD.0000000000000538