Hereditary Neuropathy - complex

Gene: ATAD3A

Green List (high evidence)

Is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy.

Neuropathy like phenotypes are only present in individuals with monoallelic variants in ATAD3A

PMID: 27640307
5 affected individuals from 5 unrelated families with the recurrent heterozygous de novo mutation (p.Arg528Trp) with all individuals presenting with symptoms of peripheral neuropathy.

Fly functional study conducted that showed a dramatic reduction in survival in the presence of the mutant protein suggesting it is highly toxic. The loss of function phenotype assiociated with bor was assessed by performing transmission electron microscopy (TEM) on the first larvae prior to their death and identified a dramatic decrease in mitochondrial content indicating a similarity in phenotype for both LoF and GoF.Therefore the mode of pathogenicity is suggestive of dominant negative.

AR inheritance is due to loss of function mutations in ATAD3A and is typically infantile onset.

Created: 1 Jun 2023, 11:42 p.m. | Last Modified: 1 Jun 2023, 11:42 p.m.

Panel Version: 0.166

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Harel-Yoon Syndrome (MIM#6173183)

Publications

• 27640307

Mode of pathogenicity
Other