Journal
EPILEPSIA
Volume 57, Issue 1, Pages E18-E23Publisher
WILEY
DOI: 10.1111/epi.13257
Keywords
De novo mutation; DNM1; Epileptic encephalopathy
Categories
Funding
- Japan Agency for Medical Research and Development (AMED)
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science (JSPS)
- Japan Science and Technology Agency (JST)
- Takeda Science Foundation
- Yokohama Foundation for Advancement of Medical Science
- Hayashi Memorial Foundation for Female Natural Scientists
- Grants-in-Aid for Scientific Research [26330331, 24118001, 24118005] Funding Source: KAKEN
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Dynamin 1 (DNM1) is a large guanosine triphosphatase involved in clathrin-mediated endocytosis. In recent studies, de novo mutations in DNM1 have been identified in five individuals with epileptic encephalopathy. In this study, we report two patients with early onset epileptic encephalopathy possessing de novo DNM1 mutations. Using whole exome sequencing, we detected the novel mutation c.127G>A (p.Gly43Ser) in a patient with Lennox-Gastaut syndrome, and a recurrent mutation c.709C>T (p.Arg237Trp) in a patient with West syndrome. Structural consideration of DNM1 mutations revealed that both mutations would destabilize the G domain structure and impair nucleotide binding, dimer formation, and/or GTPase activity of the G domain. These and previous cases of DNM1 mutations were reviewed to verify the phenotypic spectrum. The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, and hypotonia. Most cases showed development delay before the onset of seizures. A patient carrying p.Arg237Trp in this report showed a different developmental status from that of a previously reported case, together with characteristic extrapyramidal movement.
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