Early onset or syndromic epilepsy
Gene: GNAO1
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Animal model data thus suggest that pathogenic monoallelic GNAO1 mutations in humans may also result in a gain-of-function effect. AD EIEE 17. Onset of intractable seizures in first few weeks/months of life. Nakamura et al, 2013 - 4 unrelated girls EIEE - 4 diff de novo het variants. One patient was somatic mosaic. In vitro functional expression studies showed that 3 of the mutations caused impaired protein localisation to the plasma membrane, and electrophysiologic analysis showed that 3 of the mutations caused decreased GNAO1-mediated inhibition of calcium currents by norephrine compared to wt. Saitsu et al, 2017 - 2 unrelated patients - de novo het missense mutations.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epileptic encephalopathy, early infantile, 17,615473; Neurodevelopmental disorder with involuntary movements,617493
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on phenotypes: Sources: G2P and OMIM.Created: 5 Jan 2016, 12:01 p.m.
Comment on mode of inheritance: Checked the imprinted gene list, G2P and OMIM.Created: 5 Jan 2016, noon
Source Wessex and West Midlands GLH was added to GNAO1.
Source NHS GMS was added to GNAO1.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to GNAO1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to GNAO1. Panel: Genetic Epilepsy Syndromes
GNAO1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Radboud University Medical Center, Nijmegen
GNAO1 was created by Sarah Leigh