Ataxia and cerebellar anomalies - narrow panel

Gene: ATAD3A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.

Panel Version: 3.30

Green List (high evidence)

Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update - the number of unrelated families (at least 7) with cerebellar/pontocerebellar hypoplasia and biallelic SNVs in ATAD3A reaches the threshold for inclusion on this panel.

Created: 5 Jul 2021, 2:29 p.m. | Last Modified: 5 Jul 2021, 2:32 p.m.

Panel Version: 2.219

ATAD3A is associated with Harel-Yoon syndrome (MIM# 617183) with both dominant and recessive patterns of inheritance. However, only families with the biallelic form displayed cerebellar atrophy (PMID: 27640307; 32607449; 33845882). Brain MRI results have been normal in heterozygous cases to date (MOI set to 'Biallelic' only).

Furthermore, biallelic variants in ATAD3A are also associated with another phenotype comprising neonatal lethal pontocerebellar hypoplasia (MIM# 618810) - at least 13 unrelated families in literature, including 2 families with SNVs (PMID: 29053797; 31727539) and 11 families with deletions affecting ATAD3A (PMID: 27640307; 28549128; 29053797; 33845882)

Created: 5 Jul 2021, 2:17 p.m. | Last Modified: 5 Jul 2021, 2:33 p.m.

Panel Version: 2.219

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810

Publications

• 27640307
• 28549128
• 29053797
• 31727539
• 32607449
• 33845882

Comment on list classification: Based on current information in the literature in view of the number of cases with Cerebellar hypoplasia verses the there is not enough evidence to support gene-disease association rating of this gene to Green. Added watchlist tag.

Created: 8 Mar 2019, 3:10 p.m.

Green List (high evidence)

Cerebellar hypoplasia reported in 2/7 families (PMID:27640307).
Sources: Expert Review

Created: 29 Jan 2019, 2:39 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Harel-Yoon syndrome 617183

Publications

• 27640307

Variants in this GENE are reported as part of current diagnostic practice