Early onset or syndromic epilepsy
Gene: CHRNA2
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
Missense mutations have been reported to cause ADNFLE, however, the aetiology of disease could be variants specific (both GOF and LOF mechanisms have been suggested). AD Nocturnal frontal lobe epilepsy 4. Aridion et al, 2006 - in all 10 aff members of a Sardinian family - het missense variant, 1 unaff family member carried the variant - suggest incomplete penetrance. Conti et al, 2015 - 7 aff members of a large family (6 with seizures) - het missense variant. In vitro functional expression studies in HEK293 cells showed that the het mutation resulted in a reduction in current denisty to ~40%. Trivisano et al, 2015 - het missense variant - segregated with disorder in the family (father and 2 daughters).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, type 4,610353
Publications
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: It is appropriate for CHRNA2 to be green on this merged epileptic panel.Created: 9 Apr 2018, 9:14 a.m.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in unrelated cases. CHRNA2 had previously been reviewed as red because the particular phenotype was not relevant to the individual epileptic panel, however, it is appropriate for it to be green on this merged epileptic panel.Created: 9 Apr 2018, 9:01 a.m.
Variants in CHRNA2 do not appear to be associated with autosomal dominant nocturnal frontal lobe epilepsy in Chinese population.Created: 11 Dec 2017, 3:06 p.m.
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, nocturnal frontal lobe, type 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, nocturnal frontal lobe, type 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, nocturnal frontal lobe, type 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Insufficient data currentlyCreated: 8 Feb 2016, 2:48 a.m.
Comment on list classification: Discussion amoungst reviewers by email concluded that this should be rated red. In gene2phenotype it is a possible DD gene, associated with autosomal dominant nocturnal frontal lobe epilepsy.Created: 17 Dec 2015, 3:19 p.m.
Comment on mode of inheritance: Checked the imprinted gene list.Created: 17 Dec 2015, 3:14 p.m.
Causes a different seizure phenotypeCreated: 16 Dec 2015, 10:24 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epilepsy, nocturnal frontal lobe, type 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to CHRNA2.
Source NHS GMS was added to CHRNA2.
Richard Scott: Causes a different seizure phe
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to CHRNA2. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to CHRNA2. Panel: Genetic Epilepsy Syndromes
This gene has been classified as Green List (High Evidence).
CHRNA2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert
CHRNA2 was created by Sarah Leigh