Childhood onset dystonia, chorea or related movement disorder

Gene: TMEM151A

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: 4 May 2024, 6:04 p.m. | Last Modified: 4 May 2024, 6:15 p.m.

Panel Version: 4.3

Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD with onset in childhood/ adolescence. Hence, this gene can be rated Green in the next major update.

Created: 27 Jul 2023, 7:55 p.m. | Last Modified: 27 Jul 2023, 7:57 p.m.

Panel Version: 3.21

PMID:34518509 - Nine individuals from three unrelated Chines families with paroxysmal kinesigenic dyskinesia (PKD) were identified with autosomal dominant variants in TMEM151A gene. In addition, 8 unrelated patients (isolated cases) with sporadic occurrence of PKD were also identified with heterozygous variants, of which three patients inherited variants from an unaffected parent, suggesting incomplete penetrance. The age of onset of symptoms ranged between 9 and 15 years. In addition, supporting mouse model and in vitro functional assays suggested loss of function as the mechanism of disease.

PMID:34820915 - 29 PRRT2-negative Chinese patients from 25 families with PKD identified with 24 heterozygous variants in TMEM151A gene. The mean age of onset of symptoms was 12.93 years, with 13 patients reported with spontaneous remission of the disease around 21 years of age.

PMID:35587630 - De novo missense variant in TMEM151A was identified in a French man with PKD and he presented with brief attacks of dystonia after 16 years of age.

PMID:35707035 - Screening of patients with PRRT2-negative PKD and other movement disorders identified two novel variants in TMEM151A gene in two patients with PKD.

PMID:35727387 - Heterozygous missense variant was identified in four affected members of a 3-generation Chinese family with PKD and the variant segregated with the disorder in the family.

PMID:36724570 - Three patients presenting with PKD were identified with different TMEM151A variants.

This gene has been associated with relevant phenotype in OMIM (MIM #620245), but not in Gene2Phenotype.

Created: 27 Jul 2023, 7:46 p.m. | Last Modified: 27 Jul 2023, 7:51 p.m.

Panel Version: 3.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Episodic kinesigenic dyskinesia 3, OMIM:620245

Publications

• 34518509
• 34820915
• 35587630
• 35707035
• 35727387
• 36724570

Green List (high evidence)

LOF variants have been shown to cause autosomal dominant Episodic kinesigenic dyskinesia 3
Sources: NHS GMS

Created: 14 Jul 2023, 9:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Episodic kinesigenic dyskinesia 3

Publications

• 34518509
• 35707035
• 36724570
• 34820915