Early onset or syndromic epilepsy
Gene: GPHN
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
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
PMID: 24561070 - suggest haploinsufficiency and dominant negative interactionsCreated: 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
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.
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
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: GPHN were changed from Molybdenum cofactor deficiency C, OMIM:615501 to Molybdenum cofactor deficiency C, OMIM:615501; Developmental and epileptic encephalopathy, MONDO:0100062
Publications for gene: GPHN were set to 26613940; 12684523; 11095995; 22040219; 24561070; 23393157
Phenotypes for gene: GPHN were changed from Molybdenum cofactor deficiency C, 615501 to Molybdenum cofactor deficiency C, OMIM:615501
Publications for gene: GPHN were set to 26613940; 12684523; 11095995; 22040219; 24561070
Mode of inheritance for gene: GPHN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GPHN were set to 26613940; 12684523; 11095995
Source Wessex and West Midlands GLH was added to GPHN.
Source NHS GMS was added to GPHN.
Zornitza Stark: Seizures are a key part of the
Gene: gphn has been classified as Green List (High Evidence).
Gene: gphn has been classified as Green List (High Evidence).
Publications for gene: GPHN were set to
Mode of inheritance for gene: GPHN was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPHN were changed from to Molybdenum cofactor deficiency C, 615501
Expert Review Amber was added to GPHN. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to GPHN. Panel: Genetic Epilepsy Syndromes
GPHN was added to Genetic Epilepsy Syndromes panel. Sources: Expert,Expert Review Red
GPHN was created by Sarah Leigh