Early onset or syndromic epilepsy

Gene: WDR45B

Green List (high evidence)

At least three unrelated families reported (five in total), majority of individuals have had seizures, this gene fulfils criteria for Green rating.

Created: 26 Jan 2020, 6:53 a.m. | Last Modified: 26 Jan 2020, 6:53 a.m.

Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, MIM# 617977

Publications

• 21937992
• 28503735
• 27431290

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

I don't know

AR Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures (are in most patients). 1 missense and 2 nonsense reported on HGMD - 1 of these (nonsense) mentions epilepsy very small numbers. Suleiman et al, 2018.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977

Publications

• 28503735

I don't know

Added 'for-review' tag based on Zornitza's Green review on a gene where an Amber rating was decided at the last GLH review. Of the publications listed, PMID:28503735 (Suleiman et al) report 3 families (2 with seizures). PMID:21937992. Najmabadi et al 2011 identify WDR45B (WDR45L) as a candidate gene for ID. PMID:27431290 (Anazi et al., 2017) identified likely pathogenic alleles in WDR45B in ID individuals. Little information provided about WDR45B phenotype.

Created: 26 May 2020, 2:46 p.m. | Last Modified: 26 May 2020, 2:46 p.m.

Panel Version: 2.60

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green, and an Amber rating is appropriate. Demoted from Green to Amber.

Created: 15 Aug 2019, 9:39 a.m. | Last Modified: 15 Aug 2019, 9:39 a.m.

Panel Version: 1.227

Re-reviewed this gene when curating panel for GMS Clinical Indication R59 Early onset or syndromic epilepsy. In summary, the evidence is borderline: PMID:28503735 (Suleiman et al) report 6 individuals from 3 families with homozygous pathogenic variants in WDR45B, and 2 of the families (5 indivs) had seizures- seizures were not reported in the sole individual from family 3.

Created: 15 Aug 2019, 9:39 a.m. | Last Modified: 15 Aug 2019, 9:39 a.m.

Panel Version: 1.227

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: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Comment on phenotypes: Now (July 9th 2019) associated with a disorder in OMIM (617977).

Created: 9 Jul 2019, 3:52 p.m. | Last Modified: 9 Jul 2019, 3:52 p.m.

Panel Version: 1.145

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

Not associated with phenotype in OMIM, but as a possible G2P. At least three variants have now been reported as homozygotes in at least three families, in individuals with profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations.

Created: 12 Jun 2017, 12:58 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
individuals with profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations

Publications

• 21937992
• 28503735