Early onset or syndromic epilepsy

Gene: GNAO1

I don't know

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

Green List (high evidence)

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

• 23993195
• 28357411

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• Nakamura (2013) Saitsu (2015)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• Nakamura (2013) Saitsu (2015)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• Nakamura (2013) Saitsu (2015)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• Nakamura (2013) Saitsu (2015)

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