Tatton-Brown-Rahman syndrome is a congenital anomaly syndrome that manifests with overgrowth, macrocephaly, and characteristic facial features. This autosomal dominant disease is caused by a germline mutation in DNMT3A. Some patients with this syndrome develop mild to severe intellectual disability, which is sometimes accompanied by autism spectrum disorder or other developmental disorders. We report a Japanese patient with severe intellectual disability and autism spectrum disorder with a de novo mutation in the active domain of DNMT3A.

Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy characterized by an age-dependent evolution of drug-resistant seizures and poor developmental outcomes. Functional impairment of gamma-aminobutyric acid (GABA)ergic interneurons due to loss-of-function mutation of SCN1A is currently considered the main pathogenesis. In this study, to better understand the age-dependent changes in the pathogenesis of DS, we characterized the activity of different brain regions in Scn1a knockout rats at each developmental stage.

Dravet syndrome is known as an intractable infantile epilepsy caused by a heterozygous de novo mutation in SCN1A, with mutations being reported globally. In this study, we established 2 human induced pluripotent stem cell lines by expressing reprogramming factors, OCT3/4, SOX2, KLF4, L-MYC, LIN28 and p53 shRNA in the fibroblast skin cells of a patient with Dravet syndrome harboring the Y1102X pathogenic mutation in SCN1A. These cell lines showed pluripotency, ability for differentiation to the 3 germ layers, and normal karyotype.

Dravet syndrome (DS) is an infantile epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene encoding the α1 subunit of the voltage-gated sodium channel Nav1.1. As an in vitro model of this disease, we previously generated an induced pluripotent stem cell (iPSC) line from a patient with DS carrying a c.4933C>T (p.R1645*) substitution in SCN1A. Here, we describe developing a genome-edited control cell line from this DS iPSC line by substituting the point mutation with the wild-type residue. This artificial control iPSC line will be a powerful tool for research into the pathology of DS.

Dravet syndrome is a devastating infantile-onset epilepsy syndrome with cognitive deficits and autistic traits caused by genetic alterations in SCN1A gene encoding the α-subunit of the voltage-gated sodium channel Na(v)1.1. Disease modeling using patient-derived induced pluripotent stem cells (iPSCs) can be a powerful tool to reproduce this syndrome's human pathology. However, no such effort has been reported to date. We here report a cellular model for DS that utilizes patient-derived iPSCs.

De novo mutations in SCN1A are the most common cause of Dravet syndrome (DS), an infantile-onset epileptic encephalopathy. In this study, human induced pluripotent stem cell (hiPSC) line FUi002-A was generated from skin fibroblasts obtained from a clinically diagnosed 26-year-old male DS patient with the R1525X variant of the SCN1A gene. Skin fibroblasts were reprogrammed using OriP/EBNA-1 based episomal plasmids expressing reprogramming factors expressing OCT4, SOX2, KLF-4, L-MYC, LIN28, and p53 shRNA. The transgene-free FUi002-A showed pluripotency, three germ layer differentiation capacity in vitro, and a normal karyotype. The resulting hiPSCs were heterozygous for the mutation in the SCN1A gene.

To determine the significance of PCDH19 mutations in Japanese females with epilepsy and to delineate their phenotypes.