Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients

Ann Neurol. 2021 Jun;89(6):1248-1252. doi: 10.1002/ana.26080. Epub 2021 Apr 20.

Abstract

Brain mosaic mutations are a major cause of refractory focal epilepsies with cortical malformations such as focal cortical dysplasia, hemimegalencephaly, malformation of cortical development with oligodendroglial hyperplasia in epilepsy, and ganglioglioma. Here, we collected cerebrospinal fluid (CSF) during epilepsy surgery to search for somatic variants in cell-free DNA (cfDNA) using targeted droplet digital polymerase chain reaction. In 3 of 12 epileptic patients with known somatic mutations previously identified in brain tissue, we here provide evidence that brain mosaicism can be detected in the CSF-derived cfDNA. These findings suggest future opportunities for detecting the mutant allele driving epilepsy in CSF. ANN NEUROL 2021;89:1248-1252.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain*
  • Cell-Free Nucleic Acids / cerebrospinal fluid*
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / cerebrospinal fluid
  • Drug Resistant Epilepsy / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Mutation

Substances

  • Cell-Free Nucleic Acids