Optic neuropathy
Gene: ATAD3AComment on list classification: Promoted gene from Red to Amber based on the available literature. As not every patient with a monoallelic variant in this gene presented with optic atrophy, this gene has been rated Amber until further evidence is available.
PMID: 27640307 describes 5 patients from 5 unrelated families with the same de novo variant (c.1582 C>T, R528W). 3/5 patients have optic atrophy and 2/5 have hypertrophic cardiomyopathy (HCM). The authors have suggested that R528W exerts a dominant negative effect.
Three patients from 2 additional families have biallelic variants (1 compound heterozygous and 1 biallelic deletion of ATAD3B and ATAD3A). These 3 patients did not have optic atrophy nor HCM, but had congenital cataracts.
PMID: 28158749 describes a family with monoallelic variant (c.1064 G>A, G355D) where affected mother and son do not have optic atrophy nor HCM but have hereditary spastic paraplegia.
PMID: 31727539 describes a consanguineous family with 4 affected individuals with biallelic variant (c.1217T>G, L406R). 3/4 had congenital cataracts and 4/4 had HCM. No one had optic atrophy.Created: 24 Aug 2020, 3:07 p.m. | Last Modified: 24 Aug 2020, 3:07 p.m.
Panel Version: 2.24
Comment on mode of inheritance: Changed MOI from Both monoallelic and biallelic to Monoallelic only as it is patients with the Monoallelic form had optic atrophy (PMID: 27640307). Patients with biallelic variants had congenital cataract.Created: 14 Jul 2020, 10:14 a.m. | Last Modified: 14 Jul 2020, 10:14 a.m.
Panel Version: 2.18
Please note gene causes both a mono-allelic and a bi-allelic disorder. Optic atrophy reported in individuals with the recurrent de novo missense p.Arg528Trp only at this stage. The de novo status of this variant suggests it is functionally important in the pathogenesis of optic atrophy.Created: 16 Apr 2020, 12:22 a.m. | Last Modified: 16 Apr 2020, 12:22 a.m.
Panel Version: 2.3
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Harel-Yoon syndrome, MIM#617183
Publications
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183
Publications
Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183 to Harel-Yoon syndrome, OMIM:617183
Tag watchlist tag was added to gene: ATAD3A.
Gene: atad3a has been classified as Amber List (Moderate Evidence).
Publications for gene: ATAD3A were set to 27640307; 28652416
Mode of inheritance for gene: ATAD3A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATAD3A were set to 27640307
Phenotypes for gene: ATAD3A were changed from to Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183
Publications for gene: ATAD3A were set to
Mode of inheritance for gene: ATAD3A was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
gene: ATAD3A was added gene: ATAD3A was added to Optic neuropathy. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: ATAD3A was set to