Hereditary spastic paraplegia - childhood onsetGene: ATAD3A
Gene was reassessed following a Green review by Zornitza Stark. To date, ATAD3A has only been linked to spastic paraplegia in one family with a heterozygous variant (PMID: 28158749). Spasticity has been reported in 6/15 individuals with Harel-Yoon syndrome (MIM# 617183) associated with monoallelic and biallelic SNVs in this gene (PMID: 27640307; 32607449; 32933822; 33845882). However, the core phenotype is characterised by other features for which cases are more likely to get recognised, including psychomotor delay, hypotonia, cerebellar atrophy, neuropathy, hypertrophic cardiomyopathy, and ophthalmologic abnormalities. The HSP family did not share several of these features, indicating this is a distinct phenotype. As there is only one family with HSP, maintaining Red rating until further evidence emerges.
Created: 6 Jul 2021, 10:51 a.m. | Last Modified: 6 Jul 2021, 10:51 a.m.
Panel Version: 2.44
Harel-Yoon syndrome, OMIM:617183; Spastic paraplegia
Five unrelated families with recurrent de novo missense, p.Arg528Trp with syndromic neurodevelopmental disorder characterised by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. In addition, mother and child reported in PMID 28158749 with HSP and axonal neuropathy of childhood onset.
Created: 17 Sep 2020, 10:19 a.m. | Last Modified: 17 Sep 2020, 10:19 a.m.
Panel Version: 2.15
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Harel-Yoon syndrome, MIM# 617183
Added as a Red gene based on the available literature. There is only one case. 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.
Created: 24 Aug 2020, 3:18 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Harel-Yoon syndrome, 617183
Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, 617183 to Harel-Yoon syndrome, OMIM:617183; Spastic paraplegia
gene: ATAD3A was added gene: ATAD3A was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature Mode of inheritance for gene: ATAD3A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATAD3A were set to 28158749 Phenotypes for gene: ATAD3A were set to Harel-Yoon syndrome, 617183 Review for gene: ATAD3A was set to RED