Early onset or syndromic epilepsy

Gene: H3F3A

Green List (high evidence)

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

Created: 27 Apr 2022, 9:07 a.m. | Last Modified: 27 Apr 2022, 9:07 a.m.

Panel Version: 2.518

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bryant-Li Bhoj neurodevelopmental syndrome 1

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, 4:37 p.m. | Last Modified: 22 Dec 2020, 4:37 p.m.

Panel Version: 2.240

Currently not associated with any phenotype in OMIM, but is listed in Gene2Phenotype with a 'confirmed' disease confidence rating for 'Craniofacial with neurodevelopment disorders'.

- PMID: 33268356 (2020) - De novo missense variants identified in 33 unrelated individuals with a shared phenotype of GDD/ID, usually severe and often progressive, with mostly minor congenital anomalies. 23/28 patients showed abnormalities on brain MRI including hypoplasia/agenesis of the corpus collosum (9), cortical atrophy (6) and impaired myelination (5). Variable seizure phenotypes were reported in 17/33 cases, all early-onset where specified, mostly during infancy (latest onset at 14 years of age).

----
Another patient with a similar neurodevelopmental syndrome and a de novo variant in this gene was reported in PMID: 31942419 (2019), however there was no evidence of seizures at age 5.

Created: 22 Dec 2020, 4:34 p.m. | Last Modified: 22 Dec 2020, 4:34 p.m.

Panel Version: 2.239

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 H3F3A is H3-3A

Created: 6 Sep 2019, 3:43 p.m. | Last Modified: 6 Sep 2019, 3:43 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.

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
yet to be assigned

Publications

• 28506301

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)

There is no published evidence I can find of an association between this gene and epilepsy.

Created: 15 Aug 2018, 12:23 a.m.