title: De novo DNM1 mutations in two cases of epileptic encephalopathy.
abstract: 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.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.|Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kouga
authors.affiliation: Neurogenetics Unit, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.affiliation: Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Miyatake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.|Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D034284:Dynamin I / Q000235:genetics*; D059472:Exome; D006801:Humans; D007223:Infant; D065768:Lennox Gastaut Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D013036:Spasms, Infantile / Q000235:genetics*
chemical_list: D034284:Dynamin I
keywords: DNM1; De novo mutation; Epileptic encephalopathy