Early onset or syndromic epilepsy

Gene: GPHN

Green List (high evidence)

An additional case displaying biallelic variants in GPHN (missense mutation c.1264G>A and splice acceptor variant c.1315-2A>G) was reported with developmental and epileptic encephalopathy.

Created: 13 Dec 2022, 5:53 p.m. | Last Modified: 13 Dec 2022, 5:53 p.m.

Panel Version: 3.5

Phenotypes
Developmental and epileptic encephalopathy, MONDO:0100062

Publications

• 34617111

I don't know

Comment on mode of inheritance: Updated MOI from BIALLELIC to BOTH monoallelic and biallelic. Although OMIM records AR inheritance, a review by Tracy Lester notes PMIDs:24561070, 23393157 who report the association of hemizygous GPHN microdeletions with an epilepsy phenotype. The biallelic and monoallelic MOI matches the MOI of GPHN on the metabolism panels.

Created: 21 Oct 2019, 1:48 p.m. | Last Modified: 21 Oct 2019, 1:48 p.m.

Panel Version: 1.368

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. 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

Green List (high evidence)

PMID: 24561070 - suggest haploinsufficiency and dominant negative interactions

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

Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Molybdenum cofactor deficiency C, 615501

Publications

• 22040219
• 24561070

Comment when marking as ready: Gene is ready as there is enough evidence. All cases were selected based on the fact that patients were diagnosed with Molybdenum cofactor deficiency C or are positive for molybdenum cofactor deficiency who have a causative variant in the GPHN gene, who also have seizures. This is why PMID: 24561070, 23393157 were not included as publication sources.

Created: 23 Nov 2018, 2:40 p.m.

Comment on list classification: Promoted from amber to green. GPHN is confirmed to be associated with Molybdenum cofactor deficiency C on OMIM, with seizures listed as a phenotype; however, there is nothing listed in Gene2Phenotype.
There are 3 papers (PMID: 26613940,12684523,11095995) reporting patients who have Molybdenum cofactor deficiency C with different variants in the GPHN gene. All of these patients are of different ethnicity and all have seizures.

Created: 23 Nov 2018, 2:33 p.m.

Green List (high evidence)

Seizures are a key part of the phenotype.

Created: 14 Aug 2018, 11:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Molybdenum cofactor deficiency C, MIM#615501

Publications

• 26613940, 24561070, 23393157

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)