TMEM151A variants associated with paroxysmal kinesigenic dyskinesia

AbstractTMEM151A, located at 11q13.2 and encoding transmembrane protein 151A, was recently reported as causative for autosomal dominant paroxysmal kinesigenic dyskinesia (PKD). Here, through comprehensive analysis of sporadic and familial cases, we expand the clinical and mutation spectrum of PKD. In doing so, we clarify the clinical and genetic features of Chinese PKD patients harboringTMEM151A variants and further explore the relationship betweenTMEM151A mutations and PKD. Whole exome sequencing was performed on 26 sporadic PKD patients and nine familial PKD pedigrees withoutPRRT2 variants. Quantitative real-time PCR was used to assess the gene expression of frameshift mutantTMEM151A in a PKD patient.TMEM151A variants reported to date were reviewed. FourTMEM151A variants were detected in four unrelated families with 12 individuals, including a frameshift mutation [c.606_607insA (p.Val203fs)], two missense mutations [c.166G  >  A (p.Gly56Arg) and c.791T >  C (p.Val264Ala)], and a non-pathogenic variant [c.994G >  A (p.Gly332Arg)]. The monoallelic frameshift mutation [c.606_607insA (p.Val203fs)] may causeTMEM151A mRNA decay, suggesting a potential pathogenic mechanism of haploinsufficiency. Patients withTMEM151A variants had short-duration attacks and presented with dystonia. Our study provides a detailed clinical description of PKD patients withTMEM151A mutations and reports a new disease-causing mutation, expanding the known phenotypes caused byTMEM151A...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research