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Updated: May 27, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias
Jun-Ling Wang1, Li Cao, Xun-Hua Li
1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
Abstract:
Paroxysmal kinesigenic dyskinesias is a paroxysmal movement disorder characterized by recurrent, brief attacks of abnormal involuntary movements induced by sudden voluntary movements. Although several loci, including the pericentromeric region of chromosome 16, have been linked to paroxysmal kinesigenic dyskinesias, the causative gene has not yet been identified. Here, we identified proline-rich transmembrane protein 2 (PRRT2) as a causative gene of paroxysmal kinesigenic dyskinesias by using a combination of exome sequencing and linkage analysis. Genetic linkage mapping with 11 markers that encompassed the pericentromeric of chromosome 16 was performed in 27 members of two families with autosomal dominant paroxysmal kinesigenic dyskinesias. Then, the whole-exome sequencing was performed in three patients from these two families. By combining the defined linkage region (16p12.1-q12.1) and the results of exome sequencing, we identified an insertion mutation c.649_650InsC (p.P217fsX7) in one family and a nonsense mutation c.487C>T (p.Q163X) in another family. To confirm our findings, we sequenced the exons and flanking introns of PRRT2 in another three families with paroxysmal kinesigenic dyskinesias. The c.649_650InsC (p.P217fsX7) mutation was identified in two of these families, whereas a missense mutation, c.796C>T (R266W), was identified in another family with paroxysmal kinesigenic dyskinesias. All of these mutations completely co-segregated with the phenotype in each family. None of these mutations was identified in 500 normal unaffected individuals of matched geographical ancestry. Thus, we have identified PRRT2 as the first causative gene of paroxysmal kinesigenic dyskinesias, warranting further investigations to understand the pathogenesis of this disorder.
Insights
Researchers identified the proline-rich transmembrane protein 2 (PRRT2) gene as the cause of paroxysmal kinesigenic dyskinesias, a movement disorder. This discovery advances understanding of the condition
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Paroxysmal kinesigenic dyskinesias (PKD) is a movement disorder characterized by involuntary movements triggered by sudden voluntary actions.
- Previous research linked PKD to chromosome 16, but the specific causative gene remained elusive.
Purpose of the Study:
- To identify the causative gene for autosomal dominant paroxysmal kinesigenic dyskinesias.
- To investigate the genetic basis of PKD in families with a history of the disorder.
Main Methods:
- Genetic linkage analysis using 11 markers on chromosome 16 in 27 family members.
- Whole-exome sequencing in three patients from two families.
- Sequencing of PRRT2 exons and introns in an additional three PKD families.
Main Results:
- Identified insertion (c.649_650InsC) and nonsense (c.487C>T) mutations in the PRRT2 gene in two families.
- Confirmed PRRT2 mutations (c.649_650InsC and c.796C>T) in additional families, all co-segregating with the phenotype.
- No identified mutations in 500 unaffected individuals, confirming PRRT2's role.
Conclusions:
- Proline-rich transmembrane protein 2 (PRRT2) is identified as the first causative gene for paroxysmal kinesigenic dyskinesias.
- These findings provide a genetic basis for PKD and pave the way for understanding its pathogenesis.
