Intellectual disability - microarray and sequencing
Gene: ABAT
Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team), it has been agreed that this gene should be upgraded from Amber to Green at the next major review.Created: 25 Sep 2020, 3:53 p.m. | Last Modified: 25 Sep 2020, 3:53 p.m.
Panel Version: 3.342
Infants present with an encephalopathy, hypotonia and severe neurodevelopmental impairment. Although majority have seizures/EEG anomalies, these do not always appear to be part of the presenting phenotype. Therefore, there would be benefit in including ABAT on a diagnostic ID panel to ensure all cases are captured.Created: 25 Sep 2020, 3:49 p.m. | Last Modified: 25 Sep 2020, 3:49 p.m.
Panel Version: 3.341
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
GABA-transaminase deficiency, 613163
At least 5 patients from unrelated families reported in the literature, severe ID is part of the phenotypeCreated: 27 Jan 2020, 4:39 a.m. | Last Modified: 27 Jan 2020, 4:39 a.m.
Panel Version: 3.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
GABA-transaminase deficiency, MIM#613163
Publications
Variants in this GENE are reported as part of current diagnostic practice
Biallelic pathogenic variants in ABAT cause GABA-transaminase deficiency (MIM 613163).
Koenig et al. (PMID: 28411234) report on 10 affected individuals and note that all patients presented with profound neurodevelopmental impairment (age at last follow-up >7-8y for 4 subjects who fulfilled criteria for ID). Some individuals in the article by Koenig however deceased early.
OMIM mentions severe psychomotor retardation among the features.
ABAT is not associated with any phenotype in G2P.
This gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).
Perhaps it could be considered for inclusion in the panel as green / amber.Created: 21 Dec 2018, 12:30 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
GABA-transaminase deficiency (MIM 613163)
Publications
Variants in this GENE are reported as part of current diagnostic practice
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
Grey no evidence for ID in phenotypeCreated: 31 Oct 2017, 9:57 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_movement_disorder_list . Main mutation mechanism : NACreated: 27 Jul 2017, 4:57 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : sfari_20150206; manju_list; Nijmegen_ID_candidates; neuro_20160418_strict; NA. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 11:53 a.m.
Mode of inheritance
Unknown
Publications
Comment on list classification: Changed rating of gene from Red to Amber based on current information in the literature and external expert review, there is not enough evidence to support gene-disease association rating of this gene to Green.Created: 20 Feb 2019, 4:11 p.m.
Comment on publications: Added publications to support developmental delay phenotype and publication suggested from external expert review to support upgrading of the gene to Amber/GreenCreated: 20 Feb 2019, 3:37 p.m.
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.Created: 19 Jul 2017, 4:42 p.m.
Tag for-review was removed from gene: ABAT.
Source Expert Review Green was added to ABAT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: abat has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: ABAT.
Phenotypes for gene: ABAT were changed from GABA-transaminase deficiency, 613163 to GABA-transaminase deficiency, 613163; developmental delay
Gene: abat has been classified as Amber List (Moderate Evidence).
Publications for gene: ABAT were set to 27596361; 28411234
Publications for gene: ABAT were set to 27596361
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Expert Review Red was added to ABAT. Panel: Intellectual disability Model of inheritance for gene ABAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene ABAT was set to ['27596361']
This gene has been classified as Amber List (Moderate Evidence).
ABAT was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene
ABAT was created by BRIDGE