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De novo DNM1 mutations in two cases of epileptic encephalopathy
Author(s) -
Nakashima Mitsuko,
Kouga Takeshi,
Lourenço Charles Marques,
Shiina Masaaki,
Goto Tomohide,
Tsurusaki Yoshinori,
Miyatake Satoko,
Miyake Noriko,
Saitsu Hirotomo,
Ogata Kazuhiro,
Osaka Hitoshi,
Matsumoto Naomichi
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13257
Subject(s) - mutation , gtpase , biology , missense mutation , epilepsy , genetics , encephalopathy , exome sequencing , hypotonia , guanine nucleotide exchange factor , phenotype , intellectual disability , neuroscience , medicine , gene
Summary Dynamin 1 ( DNM 1) is a large guanosine triphosphatase involved in clathrin‐mediated endocytosis. In recent studies, de novo mutations in DNM 1 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 DNM 1 mutations revealed that both mutations would destabilize the G domain structure and impair nucleotide binding, dimer formation, and/or GTP ase activity of the G domain. These and previous cases of DNM 1 mutations were reviewed to verify the phenotypic spectrum. The main clinical features of DNM 1 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.