Intellectual disability - microarray and sequencing
Gene: RAB11A
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.
Panel Version: 4.53
Comment on list classification: Leaving the rating as amber just now, but with a recommendation of GREEN rating following GMS review. There are now 6 unrelated individuals with an intellectual disability phenotype reported and missense variants in this gene. Although there is little clinical data available the number of cases adds weight to this gene-disease association.Created: 11 Aug 2022, 5:32 p.m. | Last Modified: 11 Aug 2022, 5:32 p.m.
Panel Version: 3.1676
PMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). One was de-novo. Little patient information but both had brain anomalies and intellectual disability reported. 1 had seizures.Created: 11 Aug 2022, 5:25 p.m. | Last Modified: 13 Aug 2022, 3:18 p.m.
Panel Version: 3.1676
Additional two cases with microcephaly and brain anomalies reported in PMID: 33875846Created: 30 Oct 2021, 11:48 a.m. | Last Modified: 30 Oct 2021, 11:48 a.m.
Panel Version: 3.1396
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
microcephaly; brain anomalies; intellectual disability
Publications
Comment on list classification: Expert review provided by Konstantinos Varvagianni on PMID: 29100083 (Hamdan et al.) Four unrelated individuals identified with three different variants found. This case is a little boderline as little clinical information, no functional evidence reported and currently not associated with a phenotype in OMIM. Has been rated at probable in Gene2Phen based on this publication. Therefore rating as Amber and adding to "wachlist".Created: 30 May 2019, 11:25 a.m. | Last Modified: 17 Jul 2019, 1:54 p.m.
Panel Version: 0.201
PMID: 29100083 (Hamdan et al.) is a study on de novo mutations in individuals with developmental and epileptic encephalopathies (DEE).
One subject from this study was found to harbor a de novo missense RAB11A variant [NM_004663.4:c.244C>T or p.(Arg82Cys)]. This individual presented with epilepsy, developmental regression and severe ID.
In their cohort the authors also identified an additional individual with a de novo missense variant [(c.71A>G or p.(Lys24Arg)] who had moderate ID and abnormal EEG albeit without seizures.
De novo variants in RAB11A had previously been identified in 3 DDD study participants with ID.
The authors obtained clinical details on the 2 individuals with the p.(Ser154Leu) variant [NM_004663.4:c.461C>T]. One of them had moderate ID without seizures while the other had moderate global DD, also without seizures.
A third DDD study participant harbored another missense variant p.(Lys13Asn) [NM_004663.4:c.39A>C] as a de novo occurence. The authors did not manage to obtain clinical details although this patient was reported to have abnormalities of the nervous system in Decipher.
The features of all 4 individuals for whom clinical details were available are summarized in table 7 of the article and extensive information on each one is provided in the supplement.
Previous studies suggest that RAB11A has a role in NTRK2 and AMPA receptor recycling at the post-synaptic membrane of neurons and - as a result - in regulation of synaptic plasticity.
-----------
RAB11A is not associated with any phenotype in OMIM.
This gene is included in the DD panel of G2P, associated with epilepsy and intellectual disability (disease confidence: probable).
It is also included in gene panels for ID offered by some diagnostic laboratories.
-----------
As a result, it can be considered for inclusion in this panel as amber or possibly green (3 unrelated individuals with ID, 1 further with DD).
Sources: LiteratureCreated: 25 Dec 2018, 10:22 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Global developmental delay; Intellectual disability
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag gene-checked tag was added to gene: RAB11A.
Tag watchlist was removed from gene: RAB11A. Tag Q3_22_rating was removed from gene: RAB11A.
Source NHS GMS was added to RAB11A. Source Expert Review Green was added to RAB11A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: rab11a has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: RAB11A were changed from Global developmental delay; Global developmental delay, Intellectual disability; Intellectual disability to Global developmental delay, HP:0001263; Intellectual disability, HP:0001249
Publications for gene: RAB11A were set to 29100083
Tag Q3_22_rating tag was added to gene: RAB11A.
Tag watchlist tag was added to gene: RAB11A.
Source Expert Review was added to RAB11A. Source Expert Review Amber was added to RAB11A. Added phenotypes Global developmental delay, Intellectual disability for gene: RAB11A Rating Changed from No List (delete) to Amber List (moderate evidence)
gene: RAB11A was added gene: RAB11A was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RAB11A were set to 29100083 Phenotypes for gene: RAB11A were set to Global developmental delay; Intellectual disability Penetrance for gene: RAB11A were set to unknown Review for gene: RAB11A was set to AMBER gene: RAB11A was marked as current diagnostic