Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia

• Published in: Nature genetics Vol. 43; no. 12; pp. 1252 - 1255
• Main Authors: Chen, Wan-Jin, Lin, Yu, Xiong, Zhi-Qi, Wei, Wei, Ni, Wang, Tan, Guo-He, Guo, Shun-Ling, He, Jin, Chen, Ya-Fang, Zhang, Qi-Jie, Li, Hong-Fu, Lin, Yi, Murong, Shen-Xing, Xu, Jianfeng, Wang, Ning, Wu, Zhi-Ying
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/737; 692/699/375/346; Adolescent; Agriculture; Amino acids; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Cancer Research; Case-Control Studies; Chorea - genetics; Diagnosis; Exome; Exome sequencing; Female; Frameshift Mutation; Fundamental and applied biological sciences. Psychology; Gene Components; Gene Frequency; Gene Function; Genes; Genetic aspects; Genetic Association Studies; Genetic Linkage; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genomics; Heredity; Human Genetics; Humans; INDEL Mutation; letter; Male; Medical sciences; Membrane Proteins; Mice; Mice, Inbred C57BL; Movement disorders; Mutation; Nerve Tissue Proteins; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Organ Specificity; Pathogenesis; Pedigree; Protein Structure, Tertiary; Risk factors; Sequence Analysis, DNA; Spinal Cord - metabolism; Transcription, Genetic; China; Nervous system diseases; Central nervous system disease; Identification; Mutation; Neurological disorder; Sequencing; Involuntary movement; Cerebral disorder; Extrapyramidal syndrome; Dyskinesia
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.1008

Zhi-Ying Wu and colleagues report the identification of truncating mutations in the PRRT2 gene in families with paroxysmal kinesigenic dyskinesia. PRRT2 encodes the proline-rich transmembrane protein 2. Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. Using whole-exome sequencing followed by Sanger sequencing, we identified three truncating mutations within PRRT2 (NM_145239.2) in eight Han Chinese families with histories of paroxysmal kinesigenic dyskinesia: c.514_517delTCTG (p.Ser172Argfs*3) in one family, c.649dupC (p.Arg217Profs*8) in six families and c.972delA (p.Val325Serfs*12) in one family. These truncating mutations co-segregated exactly with the disease in these families and were not observed in 1,000 control subjects of matched ancestry. PRRT2 is a newly discovered gene consisting of four exons encoding the proline-rich transmembrane protein 2, which encompasses 340 amino acids and contains two predicted transmembrane domains. PRRT2 is highly expressed in the developing nervous system, and a truncating mutation alters the subcellular localization of the PRRT2 protein. The function of PRRT2 and its role in paroxysmal kinesigenic dyskinesia should be further investigated.