Early onset or syndromic epilepsy

Gene: CSNK2B

As a result of watchlist tag audit the watchlist tag was removed from CSNK2B- this is now a green gene with sufficient evidence/review

Created: 13 Jan 2020, 1:32 p.m. | Last Modified: 13 Jan 2020, 1:32 p.m.

Panel Version: 2.0

Green List (high evidence)

Appears to be associated with epilepsy but only a small number of variants reported to date.

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
Intellectual disability with or without myoclonic epilepsy

Publications

• 28762608
• 28585349

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: Alison Callaway and John Taylor. 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

Comment on list classification: Updated rating from Amber to Green based on recent 2019 paper, PMID:30655572, which reports two further unrelated cases (Japanese and Malaysian) of de novo CSNK2B variants in patients with epilepsy. Although CSNK2B is still not associated with a disorder in OMIM or Gene2Phenotype, this takes the count from two to four cases (from 3 different papers) and is therefore sufficient for a Green rating on this panel.

Created: 27 Jun 2019, 4:19 p.m. | Last Modified: 27 Jun 2019, 4:19 p.m.

Panel Version: 1.79

PMID:30655572: Nakashima et al, 2019 describe 4 patients with ID, DD and seizures. Two of the patients had variants in CSNK2B: c.533_534insGT, p.(Pro179Tyrfs*49) in Malaysian Patient 3, and c.494A>G, p.(His165Arg) in Japanese Patient 4. Both had seizures within 2 months of age. Both variants occurred de novo. In each patient, only 1 likely candidate variant was proposed. Functional assays suggested that Pro179Tyrfs*49 mutant protein was produced but showed disrupted interaction with CSNK2A1.

Created: 27 Jun 2019, 4:16 p.m. | Last Modified: 27 Jun 2019, 4:16 p.m.

Panel Version: 1.78

Comment when marking as ready: Marked as Ready: November 19th 2018.

Created: 19 Nov 2018, 8:36 p.m.

Added watchlist tag.

Created: 19 Nov 2018, 8:35 p.m.

Comment on list classification: Kept rating as Amber: As summarised by Zornitza, currently 2 epileptic patients with de novo CSNK2B variants (PMID:28762608 and PMID:28585349). The third patient was reported with intellectual disability but not epilepsy. At least one further epileptic case required for diagnostic rating.

Created: 19 Nov 2018, 8:35 p.m.

PMID:28585349 (Poirier et al., 2017) report 2 individuals with ID: Patient 2 exhibited myoclonic epilepsy whereas Patient 1 did not. Two different de novo splice-site variants in CSNK2B were identified in the patients (c.175+2T>G in the patient with epilepsy).

PMID:28762608 (Sakaguchi et al 2017) report a further epileptic patient: a male with ID and myoclonic epilepsy beginning during infancy who was found to have a de novo frameshift variant in CSNK2B (SCV000583466.1).

Created: 19 Nov 2018, 8:33 p.m.

Green List (high evidence)

Three unrelated patients reported with de novo truncating variants in this gene, two of the three had myoclonic epilepsy.

Created: 12 Aug 2018, 5:55 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myoclonic epilepsy and intellectual disability

Publications

• 28762608, 28585349

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