News Releases & Research Results Identification of the gene responsible for progressive myoclonic epilepsy

The results of collaborative study conducted by Researchers Kohei Hamanaka, Eri Imagawa, and Eriko Koshimizu and Professor Naomichi Matsumoto of the Department of Human Genetics, Yokohama City University Graduate School of Medicine, Dr. Jun Tohyama of National Hospital Organization Nishi-Niigata Chuo National Hospital, Professor Takanori Yamagata and Dr. Akihiko Miyauchi of the Department of Pediatrics, Jichi Medical University, Dr. Nina Ekhilevitch of The Genetics Institute Rambam Health Care Campus, and Drs. Ahmad Rithauddin Mohamed and Gaik-Siew Ch'ng of Kuala Lumpur Hospital.

• Mutations in the "SEMA6B gene" involved in the suppression of neurite elongation (*1) were demonstrated to cause progressive myoclonic epilepsy (*2) by whole exome sequencing analysis.
  * 1: Elongation of neurites to a target site through communication with surrounding cells.
  * 2: Progressive diseases characterized by myoclonus (involuntary movements), epileptic seizures, cerebellar symptoms, and cognitive dysfunction.
• A "SEMA6B gene" mutant, prepared using zebrafish, was tested as an experimental animal model, demonstrating reduced nerve cells in the central nervous system and enhanced epileptic seizures.
• The results of study should contribute to the molecular diagnosis and elucidation of the pathological mechanism of progressive myoclonic epilepsy and the development of medical management and treatment methods.

This study was conducted with the support of Practical Research Project for Rare/Intractable Diseases by AMED.

The results of study were published online in American Journal of Human Genetics on March 13.

Hamanaka K., et al. De novo truncating variants in the last exon of SEMA6B cause progressive myoclonic epilepsy The American Journal of Human Genetics
DOI：10.1016/j.ajhg.2020.02.011