Tmem151a-KO Mouse

TMEM151A, encoding transmembrane protein 151A, is located at 11q13.2. Currently, its essential function, associated pathways remain not comprehensively understood, but studies on its variants suggest its significance in human health, especially regarding movement-related functions. Genetic models could potentially aid in further elucidating its biological importance [2].

Mutations in TMEM151A have been found to cause paroxysmal kinesigenic dyskinesia (PKD), a type of paroxysmal dyskinesias. In a large-sample study, 24 heterozygous variants (18 missense and 6 nonsense mutations) were detected in 25 of 521 probands (frequency = 4.80%) [1]. Another study identified four TMEM151A variants in four unrelated families, with a monoallelic frameshift mutation potentially causing mRNA decay and suggesting haploinsufficiency as a pathogenic mechanism [2]. A novel heterozygous variant in TMEM151A was found in a family where some individuals had PKD with infantile convulsions, suggesting the gene may be associated with a disease spectrum including PKD-PKD/IC-BFIC [3]. Additionally, new TMEM151A variants were identified in PKD patients, and it was observed that compared with PRRT2-related PKD, TMEM151A-related PKD were more common in sporadic cases with a pure phenotype, and patients with TMEM151A variants had different features such as shorter-duration dystonia attacks, no history of benign infantile epilepsy, and residual attacks/aura when treated with certain medications [1,4].

In conclusion, TMEM151A is associated with paroxysmal kinesigenic dyskinesia. Studies on its variants in human patients have expanded the understanding of the genotypic spectrum of PKD. The discovery of TMEM151A-related PKD broadens the knowledge of the genetic causes of this movement disorder, and further functional studies, potentially including gene knockout or conditional knockout mouse models, are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD.