Childhood onset dystonia, chorea or related movement disorder

Gene: ATP5G3

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 6:27 p.m. | Last Modified: 30 Jan 2023, 6:29 p.m.

Panel Version: 2.10

Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). There is sufficient evidence to rate this gene as Green at the next GMS panel update - at least four unrelated families with heterozygous variants primarily presenting with dystonia or related movement disorder (PMID: 34636445; 34954817); also supportive Drosophila model described.

Created: 25 Aug 2022, 9:41 a.m. | Last Modified: 25 Aug 2022, 9:41 a.m.

Panel Version: 1.248

Green List (high evidence)

Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels
Sources: Literature

Created: 3 Feb 2022, 9:53 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dystonia, early-onset, and/or spastic paraplegia, MIM# 619681

Publications

• 34636445
• 34954817