Paroxysmal dyskinesia is the most prevalent kind of paroxysmal kinesigenic dyskinesia (PKD). Proline-rich transmembrane protein 2 (PRRT2) mutations are responsible for just one-third of PKD patients. For a study, researchers sought to look for a possible PKD causal gene. A total of 196 PRRT2-negative PKD patients were included in the study for whole-exome sequencing (WES). The Gene Ranking, Identification, and Prediction Tool, a case-control study approach, was used to identify the potential genes. In addition, Sanger sequencing was used to test another 325 PRRT2-negative PKD probands.

Transmembrane Protein 151 (TMEM151A) mutations were mostly grouped when patients with PKD were compared to control groups. In 25 of 521 probands, 24 heterozygous variations were found (frequency = 4.80%), comprising 18 missense and 6 nonsense mutations. The male to female ratio in 29 individuals with TMEM151A mutations was 2.63:1, and the mean age of onset was 12.93± 3.15 years. TMEM151A-related PKD was more prevalent in sporadic PKD patients with pure phenotype than PRRT2 mutation carriers. There was no statistically significant difference in attack types or treatment outcomes between the TMEM151A-positive and PRRT2-positive groups.

They aggregated mutations in TMEM151A that cause PKD using case-control analysis of large-scale WES data, broadening the genotypic range of PKD. TMEM151A-related PKD was more prevalent in sporadic cases and had a pure phenotype with a late start. Extensive functional research is required to understand the pathophysiology of TMEM151A-related PKD further. 

Reference:movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28865