Early onset or syndromic epilepsy

Gene: H3F3B

Green List (high evidence)

Agree with prev review to reclassify as green and inheritance monoallelic.

Created: 27 Apr 2022, 9:06 a.m. | Last Modified: 27 Apr 2022, 9:06 a.m.

Panel Version: 2.518

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bryant-Li Bhoj neurodevelopmental syndrome 2

Publications

• 33268356

Green List (high evidence)

Comment on list classification: Upgraded from Red to Amber, but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag) in view of evidence in recent publication (PMID: 33268356)

Created: 22 Dec 2020, 5:18 p.m. | Last Modified: 22 Dec 2020, 5:18 p.m.

Panel Version: 2.244

Currently not associated with any phenotype in OMIM or Gene2Phenotype.

- PMID: 33268356 (2020) - De novo missense variants identified in 13 unrelated individuals with a shared phenotype of GDD/ID, usually severe and often progressive, with mostly minor congenital anomalies. One individual was reported to have a normal IQ at 15 years. 8/13 patients showed abnormalities on brain MRI including hypomyelination (5), cortical atrophy (4), arachnoid cysts (3), and a thin corpus collosum (2). Variable seizure phenotypes were reported in 6/13 cases, all early-onset where specified, mostly during infancy (latest onset at 10 years of age).

Created: 22 Dec 2020, 5:17 p.m. | Last Modified: 22 Dec 2020, 5:17 p.m.

Panel Version: 2.243

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay; Intellectual disability; Neurodegeneration; Epilepsy; Facial dysmorphism; Congenital anomalies

Publications

• 33268356

Added new-gene-name tag, new approved HGNC gene symbol for H3F3B is H3-3B

Created: 6 Sep 2019, 3:52 p.m. | Last Modified: 6 Sep 2019, 3:52 p.m.

Panel Version: 1.263

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: Red.

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

Panel Version: 1.189

Red List (low evidence)

According to panel app not reported in the lit - 2 SNVs in clinvar submitted as VUS's - both individuals had dev delay and seizures.

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

Panel Version: 1.188

Mode of inheritance
Unknown

Phenotypes
schizophrenia

Publications

• 29529098

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

Comment on list classification: Based on expert reviewers' comments

Created: 6 Dec 2018, 2:46 p.m.

Red List (low evidence)

I cannot find any published evidence either. Only two SNVs in ClinVar submitted as variants of uncertain significance. Both individuals had DD/ID and seizures :
https://www.ncbi.nlm.nih.gov/clinvar/variation/521247/#supporting-observations
https://www.ncbi.nlm.nih.gov/clinvar/variation/521569/#supporting-observations .

The literature cited in these submissions is very general.

Created: 15 Aug 2018, 9:10 a.m.

Red List (low evidence)

I can't find published evidence to link this gene with epilepsy.

Created: 15 Aug 2018, 12:28 a.m.