Early onset or syndromic epilepsy

Gene: CHRNB2

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)

To date, missense variants have been reported to cause ADNFLE. AD Nocturnal frontal lobe epilepsy 3. On HGMD Pro - several variants associated with this phenotype. Paper by Hoda et al, 2008, states that almost all the causative variants in CHRNA4 and CHRNB2 are located in TM2 - the major ion poreforming domain of the receptor. Nichols et al 2016 - functional work done.

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
Epilepsy, nocturnal frontal lobe, 3,605375

Publications

• 11104662
• 25717303

Mode of pathogenicity
loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Comment on list classification: Appropriate for CHRNB2 to be green on this broad epilepsy panel

Created: 9 Apr 2018, 9:32 a.m.

Green List (high evidence)

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

Phenotypes
Epilepsy, nocturnal frontal lobe, 3

Publications

• De Fusco et al (2001) Nature Genet 26: 275-276

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

Phenotypes
Epilepsy, nocturnal frontal lobe, 3

Publications

• De Fusco et al (2001) Nature Genet 26: 275-276

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

Phenotypes
Epilepsy, nocturnal frontal lobe, 3

Publications

• De Fusco et al (2001) Nature Genet 26: 275-276

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

Green List (high evidence)

Upgraded to green following the expert review (Prof. Sisodiya) and literature revision: two families described with Epilepsy, nocturnal frontal lobe, and good functional evidence in murine models carrying the mutation

Created: 12 Jun 2017, 9:52 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, nocturnal frontal lobe, 3 605375

Publications

• 11062464
• 11104662

Red List (low evidence)

Insufficient data currently

Created: 8 Feb 2016, 2:48 a.m.

Comment on list classification: The reviewers agreed later by email that this gene should be red as it is related to frontal lobe epilepsy.

Created: 29 Jan 2016, 11:43 a.m.

Red List (low evidence)

Causes a different seizure phenotype

Created: 12 Nov 2015, 2:58 p.m.

Phenotypes
Epilepsy, nocturnal frontal lobe, 3

Publications

• De Fusco et al (2001) Nature Genet 26: 275-276

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