Early onset or syndromic epilepsy
Gene: RALGAPA1
Wagner et al 2020 - bialleleic RALGAPA1 variants in 4 unrelated individuals with profound neurodevelopmental disability, muscular hypotonia, feeding abnormalities, recurrent fever episodes and infantile spasms. Dysplasia of corpus callosum and characteristic facial features appear to be unifying features. 3/4 had infantile spasms between the ages of 8 and 12 months. RALGAA1 was absent in the fibroblasts derived from 2 affected individuals siggesting a LOF effect of these variants. Consequently RalA activity was increased in these cell lines, which is in keeping with the idea that RALGAPA1 deficiency causes a constitutive activation of RalA. Additionally, levels of RALGAPB, a scaffolding subunit of the RalGAP complex, were dramatically reduced, indicating a dysfunctional RalGAP complex.Created: 31 Jan 2021, 8:15 p.m. | Last Modified: 31 Jan 2021, 8:15 p.m.
Panel Version: 2.281
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).Created: 20 Oct 2020, 4:06 p.m. | Last Modified: 20 Oct 2020, 4:06 p.m.
Panel Version: 2.199
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: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for RALGAPA1-related neurodevelopmental disorder. At least 5 variants reported in at least 4 unrelated cases.Created: 23 Mar 2020, 2:32 p.m. | Last Modified: 23 Mar 2020, 2:32 p.m.
Panel Version: 2.11
Comment on phenotypes: Intellectual disability;hypotonia;infantile spasmsCreated: 23 Mar 2020, 2:21 p.m. | Last Modified: 23 Mar 2020, 2:21 p.m.
Panel Version: 2.10
Four unrelated individuals reported.
Sources: Expert listCreated: 2 Feb 2020, 11:04 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Intellectual disability; hypotonia; infantile spasms.
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: RALGAPA1.
Source Expert Review Green was added to RALGAPA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: ralgapa1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: RALGAPA1.
Gene: ralgapa1 has been classified as Green List (High Evidence).
Phenotypes for gene: RALGAPA1 were changed from Intellectual disability; hypotonia; infantile spasms. to .Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 618797
gene: RALGAPA1 was added gene: RALGAPA1 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RALGAPA1 were set to 32004447 Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms. Review for gene: RALGAPA1 was set to GREEN gene: RALGAPA1 was marked as current diagnostic