title: Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay.
abstract: De novo GNAO1 variants have been found in four patients including three patients with Ohtahara syndrome and one patient with childhood epilepsy. In addition, two patients showed involuntary movements, suggesting that GNAO1 variants can cause various neurological phenotypes. Here we report an additional four patients with de novo missense GNAO1 variants, one of which was identical to that of the previously reported. All the three novel variants were predicted to impair Gαo function by structural evaluation. Two patients showed early-onset epileptic encephalopathy, presenting with migrating or multifocal partial seizures in their clinical course, but the remaining two patients showed no or a few seizures. All the four patients showed severe intellectual disability, motor developmental delay, and involuntary movements. Progressive cerebral atrophy and thin corpus callosum were common features in brain images. Our study demonstrated that GNAO1 variants can cause involuntary movements and severe developmental delay with/without seizures, including various types of early-onset epileptic encephalopathy.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.identifier: http://orcid.org/0000-0003-0723-0960
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Fukai
authors.affiliation: The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.|Sackler School of Medicine, Tel Aviv University, Tel aviv, Israel.
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben-Zeev
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Mimaki
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Yukifumi
authors.initials: Y
authors.lastname: Monden
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.affiliation: The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Tziperman
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Torio
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akamine
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.affiliation: Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
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: Mitsuko
authors.initials: M
authors.lastname: Nakashima
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 Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
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: 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; D017668:Age of Onset; D000595:Amino Acid Sequence; D000818:Animals; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020820:Dyskinesias / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004569:Electroencephalography; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D016415:Sequence Alignment; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: C584143:GNAO1 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go