Early onset or syndromic epilepsy
Gene: AP1G1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.
Panel Version: 3.29
Comment on list classification: New gene added by Zornitza Stark. Usmani et al., 2021 (PMID: 34102099) identified 9 families with heterozygous and 2 families with homozygous variants in this gene. All individuals (12) had GDD and ID of various severity (mild to severe), except one patient who died at 22 days. Other features include hypotonia (9/10), seizures (6/10) and spasticity (4/10). Some supportive functional data included.
There is sufficient evidence to promote this gene to Green at the next GMS panel update, with 'monoallelic' MOI. Biallelic cases would still be picked up by the Genomics England pipeline - but this may be reviewed if additional cases are discovered.Created: 21 Sep 2021, 1:17 p.m. | Last Modified: 21 Sep 2021, 1:17 p.m.
Panel Version: 3.1292
Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.
Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.
Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.
All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
GREEN for mono-allelic, AMBER for bi-allelic.
Sources: LiteratureCreated: 7 Aug 2021, 7:39 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_21_rating was removed from gene: AP1G1.
Source Expert Review Green was added to AP1G1. Source NHS GMS was added to AP1G1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: AP1G1 was added gene: AP1G1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review Amber Q3_21_rating tags were added to gene: AP1G1. Mode of inheritance for gene: AP1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: AP1G1 were set to 34102099 Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy