2. Academic Validation
  3. De novo NSF mutations cause early infantile epileptic encephalopathy

De novo NSF mutations cause early infantile epileptic encephalopathy

  • Ann Clin Transl Neurol. 2019 Nov;6(11):2334-2339. doi: 10.1002/acn3.50917.
Hisato Suzuki 1,  Takeshi Yoshida 2,  Naoya Morisada 3,  Tomoko Uehara 1,  Kenjiro Kosaki 1,  Katsunori Sato 4,  Kohei Matsubara 4,  Toshiyuki Takano-Shimizu 4,  Toshiki Takenouchi 5
Affiliations

Affiliations

  • 1 Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
  • 2 Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 3 Department of Clinical Genetics, Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan.
  • 4 Applied Biology and Advanced Insect Research Promotion Center, Kyoto Institute of Technology, Kyoto, Japan.
  • 5 Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
PMID: 31675180 DOI: 10.1002/acn3.50917
Abstract

N-ethylmaleimide-sensitive factor (NSF) plays a critical role in intracellular vesicle transport, which is essential for neurotransmitter release. Herein, we, for the first time, document human monogenic disease phenotype of de novo pathogenic variants in NSF, that is, epileptic encephalopathy of early infantile onset. When expressed in the developing eye of Drosophila, the mutant NSF severely affected eye development, while the wild-type allele had no detectable effect under the same conditions. Our findings suggest that the two pathogenic variants exert a dominant negative effect. De novo heterozygous mutations in the NSF gene cause early infantile epileptic encephalopathy.

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