Childhood onset dystonia, chorea or related movement disorder

Gene: MT-TT

Green List (high evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains grey. Adding this gene to this panel is not consistent with the fact that there are no other similar presenting mitochondrial genes on this panel. Mitochondrial causes of childhood dystonia and movement disorders would be best tested off other more appropriate Clinical Indications.

Created: 26 Sep 2024, 1:08 p.m. | Last Modified: 26 Sep 2024, 1:08 p.m.

Panel Version: 5.3

Comment on list classification: On 18 Aug 2020, the status of MT-TT on the Childhood onset dystonia, chorea or related movement disorder panel was changed from Red to Grey (curator removed), based on a request from NHS England that this Mitochondrial gene should be removed from the panel. Would it be relevant to promote MT-TT to Green, now that there is further evidence to support the association between MT-TT variants and human disease?

Created: 24 Jun 2024, 12:38 p.m. | Last Modified: 24 Jun 2024, 12:38 p.m.

Panel Version: 4.6

At least five MT-TT variants have been associated with human conditions, including: mitochondrial disease (MONDO:0044970); Leber optic atrophy (OMIM:535000); myoclonic epilepsy associated with ragged-red fibers (OMIM:545000); fatal infantile respiratory enzyme deficiency; inherited Diabetes Mellitus; adult onset mild mypathy and other mitochondrial diseases. The condition and severity appear to be dependent on the location of the variant whether the variant is homoplasmic or the percentage of heteroplasmy (PMID: 35808913; 32083134; 30236074; 28187756; 29760464; 22638997; 1645537). MT-TT variants are not associated with a disease in OMIM or Gen2Phen, however, the ClinGen Mitochondrial Diseases Gene Curation Expert Panel has rated association between MT-TT variants and mitochondrial disease (MONDO:0044970) as Moderate.

Created: 24 Jun 2024, 12:35 p.m. | Last Modified: 24 Jun 2024, 12:35 p.m.

Panel Version: 4.5

Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.

Created: 18 Aug 2020, 3:45 p.m. | Last Modified: 18 Aug 2020, 4:09 p.m.

Panel Version: 1.45

Red List (low evidence)