Novel variant in CHRNA4 with benign childhood epilepsy with centrotemporal spikes and contribution to precise medicine

Mol Genet Genomic Med. 2020 Jul;8(7):e1264. doi: 10.1002/mgg3.1264. Epub 2020 Apr 28.

Abstract

Background: Benign childhood epilepsy with centrotemporal spikes (BECTS) or benign rolandic epilepsy is the most common epileptic syndrome in school-age children. Genetics is an important factor in BECTS pathogenesis, and <10 genes were associated with BECTS. This study aimed to identify novel genetic causes of BECTS.

Methods: We conducted whole-exome sequencing on a patient with BECTS and validated the findings by Sanger sequencing in a pedigree with three patients.

Results: CHRNA4 c.1007G>A was identified in three patients with BECTS in a pedigree. Carbamazepine, which should be carefully used in BECTS, was observed to be effective in the treatment of our atypical BECTS proband based on the molecular diagnosis of CHRNA4.

Conclusion: This is the first study on CHRNA4 variant in BECTS, which widened the genetic spectrum of BECTS and contributed to precise medicine in BECTS.

Keywords: CHRNA4; centrotemporal; epilepsy; pedigree; rolandic.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / therapeutic use
  • Carbamazepine / administration & dosage
  • Carbamazepine / therapeutic use
  • Child
  • Child, Preschool
  • Epilepsy, Rolandic / diagnosis
  • Epilepsy, Rolandic / drug therapy
  • Epilepsy, Rolandic / genetics*
  • Female
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Precision Medicine / methods
  • Receptors, Nicotinic / genetics*

Substances

  • Anticonvulsants
  • Receptors, Nicotinic
  • nicotinic acetylcholine receptor alpha4 subunit
  • Carbamazepine