title: Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia.
abstract: 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.
authors.affiliation: Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, China.
authors.forename: Wan-Jin
authors.initials: WJ
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Wang
authors.initials: W
authors.lastname: Ni
authors.forename: Guo-He
authors.initials: GH
authors.lastname: Tan
authors.forename: Shun-Ling
authors.initials: SL
authors.lastname: Guo
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Chen
authors.forename: Qi-Jie
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Hong-Fu
authors.initials: HF
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Shen-Xing
authors.initials: SX
authors.lastname: Murong
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002819:Chorea / Q000235:genetics*; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D040461:Gene Components; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D040941:Heredity; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D010375:Pedigree; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D013116:Spinal Cord / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human
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