Polygenic Landscape of Cryptogenic New-Onset Refractory Status Epilepticus: A Comprehensive Whole-Genome Sequencing
Yoonhyuk Jang1,2,3, Sung Eun Hong4, Soo Hyun Ahn1
1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Jongno-gu, Seoul, South Korea.
Abstract:
Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201-1208.
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