Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay

• Published in: European journal of human genetics : EJHG Vol. 24; no. 1; pp. 129 - 134
• Main Authors: Saitsu, Hirotomo, Fukai, Ryoko, Ben-Zeev, Bruria, Sakai, Yasunari, Mimaki, Masakazu, Okamoto, Nobuhiko, Suzuki, Yasuhiro, Monden, Yukifumi, Saito, Hiroshi, Tziperman, Barak, Torio, Michiko, Akamine, Satoshi, Takahashi, Nagahisa, Osaka, Hitoshi, Yamagata, Takanori, Nakamura, Kazuyuki, Tsurusaki, Yoshinori, Nakashima, Mitsuko, Miyake, Noriko, Shiina, Masaaki, Ogata, Kazuhiro, Matsumoto, Naomichi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2016
• Subjects: Adolescent; Age; Age of Onset; Amino Acid Sequence; Animals; Atrophy; Brain research; Children; Childrens health; Corpus callosum; Corpus Callosum - metabolism; Corpus Callosum - pathology; Deoxyribonucleic acid; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; Developmental Disabilities - pathology; DNA; Dyskinesias - diagnosis; Dyskinesias - genetics; Dyskinesias - pathology; Electroencephalography; Encephalopathy; Epilepsy; Female; Gene Expression; Genes; Genetic testing; Genotype; GTP-Binding Protein alpha Subunits, Gi-Go - genetics; Humans; Infant; Intellectual disabilities; Maternal & child health; Medicine; Molecular Sequence Data; Mutation; Mutation, Missense; Patients; Pediatrics; Phenotype; Phenotypes; Proteins; Seizures; Sequence Alignment; Short Report; Spasms, Infantile - diagnosis; Spasms, Infantile - genetics; Spasms, Infantile - pathology; University graduates; United States > US; Japan; Israel
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2015.92

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.