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Eur J Hum Genet. 2016 Jan;24(1):129-34. doi: 10.1038/ejhg.2015.92. Epub 2015 May 13.

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

Author information

1
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
2
Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
3
The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
4
Sackler School of Medicine, Tel Aviv University, Tel aviv, Israel.
5
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
6
Department of Pediatrics, University of Tokyo, Tokyo, Japan.
7
Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
8
Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
9
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
10
Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
11
Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

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.

PMID:
25966631
PMCID:
PMC4795232
DOI:
10.1038/ejhg.2015.92
[Indexed for MEDLINE]
Free PMC Article

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