Early onset or syndromic epilepsy

Gene: CLCN6

I don't know

Comment on list classification: Changed rating from Amber to Red based on post-Webex reviews from Helen Lord and Alison Callaway: the current published association between CLCN6 and seizures is weak.

Created: 9 Sep 2019, 9:32 a.m. | Last Modified: 9 Sep 2019, 9:32 a.m.

Panel Version: 1.302

Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Red List (low evidence)

Not associated with dosease on OMIM. HGMD Pro - 4 variants listed all as DM?. Wang et al, 2017 (28074849) - de novo missense variant identified (Glu178Ala) - patient D1435 who had spasms in cluster change to tonic-clonic and myoclonic seizure - classed as likely pathogenic. Yamomoto et al (25794116) - BPEI -3 missense variants identified in CLCN6. 2 ifthese variants were found in 1 control sample (R319Q) or listed in the SNV database (V387M).

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

4 variants on HGMDPro, all 'DM?', only one associated with spasms. No associated phenotype on OMIM.

Created: 23 Aug 2019, 10:17 a.m. | Last Modified: 23 Aug 2019, 10:17 a.m.

Panel Version: 1.256

I don't know

Comment on publications: PMID 29667327 - one case with seizures, no other work up

PMID 26658788 - reference to rare traits and BP control

PMID 25794116 - three families with variants and a history of seizures. However one person with a reported phenotype of seizures was variant negative and the functional work does not look compelling

Created: 9 Jul 2019, 1:55 p.m. | Last Modified: 9 Jul 2019, 1:55 p.m.

Panel Version: 1.142

Sources: Literature

Created: 9 Jul 2019, 1:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29667327
• 26658788
• 25794116