Likely inborn error of metabolism - targeted testing not possible
Gene: ATAD3AComment on list classification: New gene added by external expert and reviewed by curation team and the clinical team: Sufficient evidence has been provided by the external expert review for this gene to be rated green.
Other aspects of the phenotype may warrant for this gene to be included on alternative specific panels (i.e. intellectual disability); however, not enough evidence is available at the moment. Therefore, this gene has also been added to the "watchlist" so that more cases can be collected.Created: 18 Mar 2019, 3 p.m.
Comment on mode of pathogenicity: There is a recurrent missense variant thought to act in a dominant negative manner.Created: 18 Mar 2019, 2:40 p.m.
Comment on mode of inheritance: As the carrier parents of the biallelic cases do not appear to have any phenotype, have given this a biallelic mode of inheritance.Created: 18 Mar 2019, 2:38 p.m.
A raised plasma lactate was reported in 4/7 families and methylglutaconic aciduria in 3/7 families (PMID: 27640307). Multiple patients with a diagnosis are described as having "severe metabolic disease".
Sources: LiteratureCreated: 29 Jan 2019, 2:27 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Lactic acidosis; Methylglutaconic aciduria; Neurological abnormalities; Cerebellar hypoplasia; Optic atrophy; Hypertrophic cardiomyopathy; Scoliosis; Spinal muscular atrophy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Report of multiple, recurrent de novo monoallelic mutations in PMID 27640307 - sufficient evidence for inclusion
One family reported with biallelic deletion (also in PMID 27640307) - await further evidenceCreated: 23 Feb 2017, 5:39 p.m.
Comment on list classification: Report of multiple, recurrent de novo monoallelic mutations in PMID 27640307 - sufficient evidence for inclusion
One family reported with biallelic deletion (also in PMID 27640307) - await further evidenceCreated: 23 Feb 2017, 5:39 p.m.
Report of multiple, recurrent de novo monoallelic mutations in PMID 27640307 - sufficient evidence for inclusion
One family reported with biallelic deletion (also in PMID 27640307) - await further evidenceCreated: 23 Feb 2017, 5:39 p.m.
Phenotypes
617183
Publications
Comment when marking as ready: No evidence for association with a mitochondrial syndrome phenotype - remains on the red list.Created: 26 Feb 2016, 12:25 p.m.
no reports of mutations in literatureCreated: 3 Feb 2016, 5:56 p.m.
Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome 617183 to Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810; Lactic acidosis; Methylglutaconic aciduria
Checked against super panel made up of the panel constituents. Ready to promote to version 1.
gene: ATAD3A was added gene: ATAD3A was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ATAD3A were set to 27640307 Phenotypes for gene: ATAD3A were set to Harel-Yoon syndrome 617183